BioLeonhardt Supporting Articles

Related Articles

Relation between microcurrent therapy and satellite cells in the regeneration of induced skeletal muscle injury in rat – Click Here

Sonic hedgehog signaling regulates the mammalian cardiac …

https://www.ncbi.nlm.nih.gov/pubmed/30236923
by H Kawagishi – ‎2018 – ‎Related articles

MicroRNA Intercellular Transfer and Bioelectrical Regulation of Model Multicellular Ensembles by the Gap Junction Connectivity

† Dept. de Termodinàmica, Facultat de Física, Universitat de València, E-46100 Burjassot, Spain
‡ Laboratory of RNA Modification and Mitochondrial Diseases, Centro de Investigación Príncipe Felipe, Valencia 46012, Spain
J. Phys. Chem. B2017121 (32), pp 7602–7613
DOI: 10.1021/acs.jpcb.7b04774
Publication Date (Web): July 17, 2017
Copyright © 2017 American Chemical Society

https://pubs.acs.org/doi/10.1021/acs.jpcb.7b04774

A current affair: electrotherapy in wound healing – NCBI – NIH

STIMULATOR, PUMP & COMPOSITION – CalXStars Business …

www.freepatentsonline.com/y2017/0266371.html

The system of claim 1, wherein the microinfusion pump is programmable. 5. ….. using bioelectricenergy, topical compositions, stem cell/growth factor micro …

 

Leonhardt Adds HIF-1 Alpha To Estate of Bioelectric Controlled …

menafn.com/…/Leonhardt-Adds-HIF-1-Alpha-To-Estate-of-Bioelectric-Controlled-Re…

Jun 9, 2017 – ‘HIF 1Alphais one of the most potent growth factors in promoting cell, … re-fillable micro infusion pump and (3) a fifteen component stem cell …

 

Leonhardt and Genovese file Patent for Bioelectric Controlled …

https://leonhardtventures.com › News › Uncategorized

Dec 16, 2016 – Leonhardt and Genovese file Patent for Bioelectric Controlled Expression of PDGF a Powerful Organ Regeneration Cytokine. Press Release ..

 

[PDF]2017 Annual Report

2ho06i23weps2hx3g346udzo-wpengine.netdna-ssl.com/…/cal-x_stars_annual-report_…

Second Heart Assist, Inc. launched with an all-star team to develop best in class devices ….BioLeonhardt Whole Body Regeneration product with a full series of …

 

Leonhardt Ventures to Present Heart and Heart Valve Regeneration …

… a combination of bioelectric stimulation controlled release of 13+ regeneration … stimulator + micro infusion pump + multi-component stem cell + growth factor …

 

Second Heart Assist, Inc. Launches Series of Preclinical Development …

Oct 19, 2017 – Second Heart Assist, Inc. Launches Series of Preclinical … for the BioLeonhardtwww.bioleonhardt.com heart regeneration implant comprised …

 

BioLeonhardt and Second Heart Assist to Present at Intl. Academy of …

mysocialgoodnews.com/bioleonhardt-second-heart-assist-present-intl-academy-cardio…

Jul 13, 2017 – BioLeonhardt and Second Heart Assist to Present at Intl. Academy of Cardiology World Congress of Heart Disease July 14th-16th Vancouver.

 

Second Heart Assist, Inc. Raises $1.0M in Series A Financing | My …

mysocialgoodnews.com/second-heart-assist-inc-raises-1-0m-series-financing/

4 days ago – Declare Your Good: JetBlue Launches… … 2, 2017 – Second Heart Assist, Inc. announced today that it raised $1.0 million in a Series A financing. … their heart with our flagship BioLeonhardt technology comprising a stem cell …

[PPT]change in polarity of stimulator changes effect to cell … – CRTOnline

www.crtonline.org/Assets/…27f8…/a9df5ceb-736f-428a-ad38-31501394ea60-pptx

Results of stem cell therapy for cardiac regeneration to date have shown … MICROINFUSION PUMP …Bioelectric Stimulation for Release of Targeted Proteins.

 

The Future for HF Therapy – American Association of Heart Failure …

www.aahfn.org/resource/resmgr/Advanced…/LMiller_Future_Therapy_Hando.pdf

Mar 1, 2017 – Stem Cell/Gene Therapy for CV Dis. … Bioelectric Stimulation … Factors Affecting Outcome of …. Programmable MICROINFUSION PUMP.

Cardiac pre-differentiation of human mesenchymal stem cells by electrostimulation – Click Here

Electrostimulation induces cardiomyocyte predifferentiation of fibroblasts – Click Here

Predifferentiated Adult Stem Cells and Matrices for Cardiac Cell Therapy – Click Here

Electrostimulated bone marrow human mesenchymal stem cells produce follistatin – Click Here

In Situ Electrostimulation Drives a Regenerative Shift in the Zone of Infarcted Myocardium – Click Here

Electrical Stimulation Technologies for Wound Healing – Click Here

Possible Local Stem Cells Activation by Microcurrent – Click Here

How Microcurrent Stimulation Produces ATP – Click Here

Improving Cardiac Cell Production through Enhancing Early Mesoderm Formation – Click Here

Electrical stimulation proven to accelerate wound healing – Click Here

Cell Therapy and Tissue Generation – Click Here

0195 : Muscular effects of electrical myostimulation in heart – Click Here

Biomimetic scaffold combined with electrical stimulation and growth factor promotes tissue engineered cardiac development.

Full Text – http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3946629/

Abstract – http://www.ncbi.nlm.nih.gov/pubmed/24240126

New therapy for heart failure may enhance body’s stem cell response at cardiovascular injury site

http://www.eurekalert.org/pub_releases/2013-02/uosf-ntf022113.php

Low current electrical stimulation upregulates cytokine expression in …
www.ncbi.nlm.nih.gov/pubmed/22006493‎ 
by L Salcedo – 2012 – Related articles
Oct 18, 2011 – SDF-1 and MCP-3 after 1 h were significantly higher than after 4 h of stimulation at both time points. CONCLUSION: Electrical stimulation for 1 h …

Cxcl12 chemokine (C-X-C motif) ligand 12 [Rattus norvegicus …
www.ncbi.nlm.nih.gov/gene/24772‎ 
Apr 29, 2013 – Electrical stimulation for 1 h significantly upregulates SDF-1 and MCP-3 … Direct anal sphincter injury results in higher levels of SDF-1 and …

Importance of the SDF-1:CXCR4 Axis in Myocardial Repair
circres.ahajournals.org/content/104/10/1133.full‎ 
by MS Penn – 2009 – Cited by 60 – Related articles
The data from this study demonstrate the importance of the SDF-1:CXCR4 axis … ofSDF-1 in the setting of ischemic cardiomyopathy has been shown to improve …

Myocardial Delivery of SDF-1 in Patients with Ischemic Heart …
circres.ahajournals.org/content/…/CIRCRESAHA.113.300902.abstract‎ 
by RJ Hajjar – 2013 – Related articles
Feb 21, 2013 – Myocardial Delivery of SDF-1 in Patients with Ischemic Heart … in a Phase 1 trial resulted in significant clinical improvements in patients with

Progenitor Cell Mobilization and Recruitment: SDF-1, CXCR4, α4 …
www.ncbi.nlm.nih.gov › Journal List › NIHPA Author Manuscripts‎
by M Cheng – 2012 – Cited by 1 – Related articles
Jan 27, 2013 – Efforts to supplement SDF-1 levels in the ischemic region may alsoimprove …. However, bone marrow progenitor cell levels were lower in c-kit ….hind-limb ischemia,176 and SDF-1 also improved cardiac function after …

Angiogenic effects of stromal cell-derived factor-1 (SDF-1/CXCL12 …
www.ncbi.nlm.nih.gov/pubmed/20206813‎
by TK Ho – 2010 – Cited by 8 – Related articles
Angiogenic effects of stromal cell-derived factor-1 (SDF-1/CXCL12) variants in …PURPOSE: Critical leg ischemia (CLI) is associated with a high morbidity and mortality. … In vivo, gastrocnemius biopsies were obtained from the lower limbs of …

Effects of moderate electrical stimulation on reactive species …
www.ncbi.nlm.nih.gov/pubmed/21898396‎
by RH Lambertucci – 2012 – Related articles
Effects of moderate electrical stimulation on reactive species production by … of a moderate electrical stimulation on superoxide and nitric oxide production by … Nitric Oxide Synthase Type II/antagonists & inhibitors; Nitric Oxide Synthase Type …

Nitric oxide synthase modulates angiogenesis in response to tissue …
www.ncbi.nlm.nih.gov/pubmed/9616228‎
by T Murohara – 1998 – Cited by 1006 – Related articles
Jun 1, 1998 – We tested the hypothesis that endothelial nitric oxide synthase (eNOS)… Angiogenesis in the ischemic hindlimb was significantly improved by .

Endothelial nitric oxide synthase is critical for ischemic remodeling …
www.pnas.org/content/102/31/10999.full.pdf‎
by J Yu – 2005 – Cited by 198 – Related articles
Aug 2, 2005 – The genetic loss of endothelial-derived nitric oxide synthase …..improved blood flow recovery at 2 and 4 weeks after ischemia (Fig. 4B).

Enhancing the Outcome of Cell Therapy for Cardiac Repair
circ.ahajournals.org/content/121/2/325.full‎
by E Chavakis – 2010 – Cited by 48 – Related articles
Indeed, local injection of SDF-1 in ischemic hind limbs increased the recruitment of …the cells for cell delivery may affect the expression levels of chemokine receptors. ….Moreover, electric stimulation influences ESC differentiation.

Functional screening identifies miRNAs inducing cardiac regeneration.
www.ncbi.nlm.nih.gov/pubmed/23222520‎
by A Eulalio – 2012 – Cited by 18 – Related articles
Dec 20, 2012 – Here we show that the exogenous administration of selectedmicroRNAs (miRNAs) markedly stimulates cardiomyocyte proliferation and

A micelle-shedding thermosensitive hydrogel as sustained release …
www.ncbi.nlm.nih.gov/pubmed/22971272‎
by AJ de Graaf – 2012 – Related articles
Aug 21, 2012 – Utrecht Institute for Pharmaceutical Sciences, Pharmaceutics, Utrecht… In this paper it is shown that when a thermosensitive hydrogel based …
Utrecht University – Technology Transfer – Collective IP
https://www.collectiveip.com/technology…/utrecht…/patents?q…‎
Collective IP has compiled all of Utrecht University’s technology transfer data. Search… The invention relates to hydrogel compositions, which can be applied as …

Effective Cardiac Myocyte Differentiation of Human Induced …
www.plosone.org/article/info:doi/10.1371/journal.pone.0053764‎
by L Ye – 2013 – Related articles
Induced pluripotent stem cells (iPSCs), cells that can differentiate into all cell types… that cardiac progenitors transplanted into hearts with MI can repair the damaged …..Reinecke H, Murry CE (2002) Taking the death toll after cardiomyocyte …

Cardiomyocyte Formation by Skeletal Muscle-Derived Multi …
www.ncbi.nlm.nih.gov › Journal List › PLoS ONE › v.3(3); 2008‎
by T Tamaki – 2008 – Cited by 33 – Related articles
Mar 12, 2008 – Tetsuro Tamaki,1,2* Akira Akatsuka,1,3 Yoshinori Okada,1,3 Yoshiyasu … previously, also give rise to cardiac muscle cells as multi-myogenic stem cells, … We first identified myogenic-vasculogenic progenitor cells in the interstitial …These findings suggest that Sk-34 cells are immature stem cells that have …

Does the Human Skeletal Muscle Harbor the Murine Equivalents of …
www.ncbi.nlm.nih.gov › Journal List › Mol Ther › v.17(4); Apr 2009‎
by S Proksch – 2009 – Cited by 5 – Related articles
Autologous skeletal myoblasts have been the first cells to enter the clinical …. The most promising candidate marker to select putative cardiac progenitor …… [PubMed];Tamaki T, Akatsuka A, Ando K, Nakamura Y, Matsuzawa H, Hotta T, et al.

Isolation and expansion of adult cardiac stem cells from human and …
www.ncbi.nlm.nih.gov/pubmed/15472116‎
by E Messina – 2004 – Cited by 853 – Related articles
Isolation and expansion of adult cardiac stem cells from human and murine heart. Messina E, De Angelis L, Frati G, Morrone S, Chimenti S, Fiordaliso F, Salio M, .

Resident cardiac stem cells.
www.ncbi.nlm.nih.gov/pubmed/22114897‎
by C Frati – 2011 – Cited by 8 – Related articles
Resident cardiac stem cells. Frati C, Savi M, Graiani G, Lagrasta C, Cavalli S, Prezioso L, Rossetti P, Mangiaracina C, Ferraro F, Madeddu D, Musso E, Stilli D, ..

Cardiac resident progenitor cells: evidence and functional significance
eurheartj.oxfordjournals.org/content/early/2012/…/eurheartj.ehs208.full‎
by K Guan – 2012 – Cited by 1 – Related articles
Jul 10, 2012 – Regenerative stem cells may be derived from extracardiac sources as well as from the heart itself. … What do we know about cardiac resident progenitor cells? ….. Messina E,; De Angelis L,; Frati G,; Morrone S,; Chimenti S, …

May 25, 2012
Gladstone Scientist Receives $6.3M Award from the California Institute for Regenerative Medicine
The California Institute for Regenerative Medicine (CIRM) has awarded Deepak Srivastava, MD—who directs cardiovascular and stem cell research at the Gladstone Institutes—a $6.3 million Early Translational Award to promote stem cell-based innovation. Dr. Srivastava will use these funds to evaluate new therapies for regenerating damaged heart muscle in a preclinical setting that could lay the foundation for human clinical trials.
April 18, 2012
Gladstone Scientists Regenerate Damaged Hearts By Transforming Scar Tissue into Beating Heart Muscle
Scientists at the Gladstone Institutes today are announcing a research breakthrough in mice that one day may help doctors restore hearts damaged by heart attacks—by converting scar-forming cardiac cells into beating heart muscle.

Electrical stimulation of partial limb regeneration in mammals.
www.ncbi.nlm.nih.gov/pubmed/4503923‎ 

by RO Becker – 1972 – Cited by 77 – Related articles
Bull N Y Acad Med. 1972 May;48(4):627-41. Electrical stimulation of partial limb regeneration in mammals. Becker RO, Spadaro JA. PMCID: PMC1806700 …


Electric switch could turn on limb regeneration : Nature News
www.nature.com/uidfinder/10.1038/news070226-8‎ 

Feb 28, 2007 – Electric switch could turn on limb regeneration … some researchers hope for new approaches to stimulating tissue regeneration in humans1

Combined autologous cellular cardiomyoplasty with skeletal …
www.ncbi.nlm.nih.gov/pubmed/16153908‎ 
by IA Memon – 2005 – Cited by 53 – Related articles
Combined autologous cellular cardiomyoplasty with skeletal myoblasts and bone marrow cells in canine hearts for ischemic cardiomyopathy. Memon IA, Sawa Y …
Combined transplantation of skeletal myoblasts and bone marrow …
www.ncbi.nlm.nih.gov/pubmed/15037282‎ 
by HC Ott – 2004 – Cited by 52 – Related articles
OBJECTIVES: To prove whether intramyocardial transplantation of combined skeletalmyoblasts (SM) and mononuclear bone marrow stem cells is superior to …
Combination Cell Therapy for Heart Failure
Full Text – Circulation
circ.ahajournals.org/content/114/1_suppl/I-120.full‎ 
by LC Guarita-Souza – 2006 – Cited by 58 – Related articles
Flow cytometric analysis was performed to identify bone marrow origin stem cells ….The idea of using a combination of skeletal myoblasts, which recolonize the ….Oliveira AS, Brofman P. Cell transplantation: differential effects of myoblasts …
Neoangiogenesis after combined transplantation of skeletal …
icvts.oxfordjournals.org/content/7/2/249.full.pdf‎ 
by N Bonaros – 2008 – Cited by 21 – Related articles
Objectives: We previously reported that combined transplantation of skeletalmyoblasts and AC-133q cells … tion of skeletal myoblasts (SM) and bone marrow-derived ….. Brofman P. Simultaneous autologous transplantation of cocultured.

Myogenic specification of side population cells in skeletal muscle.
Asakura A, Seale P, Girgis-Gabardo A, Rudnicki MA.
Source
Molecular Medicine Program, Ottawa Health Research Institute, Ottawa, Ontario, K1H 8L6 Canada.
http://www.ncbi.nlm.nih.gov/pubmed/12379804

http://www.rmutrecht.org/
RMU: Regenerative Medicine Utrecht – Homepage
www.rmutrecht.org/‎ 
Regenerative Medicine (RM) is a rapidly expanding new field that brings together fundamental and clinical scientists from multiple disciplines with the aim of ..

RMU: Regenerative Medicine Utrecht – Pieter Doevendans, MD, PhD
rmutrecht.org/research/facilities/index.php?option=com…id…‎ 
Regenerative Medicine (RM) is a rapidly expanding new field that brings together fundamental and clinical scientists from multiple disciplines with the aim of .

Phase II Study Myoblasts (Muscle Stem Cells) Heart Failure 
Dr. Eric Duckers – The Netherlands 
Click Here Slide Presentation > Control – SBHCI
sbhci.org.br/wp-content/uploads/2011/03/SEISMIC_Serruys.ppt‎
Autologous Skeletal Myoblast Transplantation. in Congestive Heart Failure Patients: The SEISMIC Trial. Patrick W. Serruys, MD PhD. Eric J Duckers, MD PhD …

In situ electrostimulation drives a regenerative shift in the zone of infarcted myocardium.

 

Angiogenic gene-modified myoblasts promote vascularization during repair of skeletal muscle defects

Sdf-1 (CXCL12) improves skeletal muscle regeneration via the mobilisation of Cxcr4 and CD34 expressing cells.

Functional regeneration of ischemic myocardium by transplanted cells overexpressing stromal cell-derived factor-1 (SDF-1): intramyocardial injection versus scaffold-based application.

Neoangiogenesis after combined transplantation of skeletal myoblasts and angiopoietic progenitors leads to increased cell engraftment and lower apoptosis rates in ischemic heart failure.

 

MODIFIED SKELETAL MYOBLAST THERAPY FOR CARDIAC FAILURE USING AAV SDF1

00579Screen Shot 2013-10-04 at 7.30.48 AM

 

The Effect of Incorporation of SDF-1α into PLGA Scaffolds on Stem Cell Recruitment and the Inflammatory Response

 

Protease-Resistant Stromal Cell–Derived Factor-1 for the Treatment of Experimental Peripheral Artery Disease

 

Efficacy of systemic administration of SDF-1 in a model of vascular insufficiency: Support for an endothelium-dependent mechanism

 

Repeated implantation of skeletal myoblast in a swine model of …
eurheartj.oxfordjournals.org/…/1013.full.pdf‎

www.ncbi.nlm.nih.gov/…/16936434

eurheartj.oxfordjournals.org/…/eurheartj.ehp

Stem cells heart – Howard Leonhardt Presenting 25 Yr Experience …

Intrafibrillar silicification of collagen scaffolds for sustained release of …
www.fasebj.org/content/early/2012/07/26/fj.12-210211.full.pdf‎

Electroacupuncture preconditioning reduces cerebral ischemic …
pubmedcentralcanada.ca/pmcc/articles/PMC3562247/‎

Continuous Delivery of Stromal Cell-Derived Factor-1 … – People Page
people.hofstra.edu/…/Continuous%20Delivery%20o…‎  

Differentiation of human adult cardiac stem cells exposed to …
cardiovascres.oxfordjournals.org/content/82/3/411.full.pdf‎

Searching for Prometheus: Cell therapy and … – Atomium Culture
atomiumculture.eu
Isolation and Expansion of Adult Cardiac Stem Cells From Human …
circres.ahajournals.org/content/95/9/911.full‎  
Cardiac stem cells: isolation, expansion and experimental … – Nature
www.nature.com

Molecular Therapy http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2835114/

Mild electrical stimulation with heat stimulation increase …
www.ncbi.nlm.nih.gov/…‎  

Mild Electrical Stimulation with Heat Shock Ameliorates …
www.plosone.org/…/info%3Adoi%2F10.1371%2Fjournal.po…‎  
PLOS ONE

Mild Electrical Stimulation and Heat Shock Ameliorates …
www.plosone.org/…/info%3Adoi%2F10.1371%2Fjournal.po…‎  

Mild electrical stimulation with heat stimulation increase …
www.tripdatabase.com/…/1416291-Mild-electrical-stimulation-with-heat-…‎

Hyperthermia With Mild Electrical Stimulation Protects …
diabetes.diabetesjournals.org/content/61/4/838.long

Fatiguing stimulation of one skeletal muscle triggers heat …
jeb.biologists.org/content/…/4041.f…‎  

Use of Implantable Pumps for Growth Factor Delivery – REFERENCES

1. Epidermal Growth Factor
Q2719 Hawryluk,G.W.J., Mothe,A., Wang,J., Wang,S., Tator,C., Fehlings,M.G. An In Vivo Characterization of Trophic Factor Production Following Neural Precursor Cell or Bone Marrow Stromal Cell Transplantation for Spinal Cord Injury. STEM CELLS AND DEVELOPMENT 2012; 21(-12-):2222-2238. >>> Epidermal growth factor; fibroblast growth factor, beta; platelet-derived growth factor, alpha; CSF/CNS (intrathecal); Rat; 1007D; 7 days; Animal info (adult, female, tg).
Q2380 Paliouras,G.N., Hamilton,L.K., Aumont,A., Joppe,S.E., Barnabe-Heider,F., Fernandes,K.J.L. Mammalian Target of Rapamycin Signaling Is a Key Regulator of the Transit-Amplifying Progenitor Pool in the Adult and Aging Forebrain. Journal of Neuroscience 2012; 32(-43-):15012-15026. >>> Rapamycin; epidermal growth factor; DMSO; CSF/CNS; Mice (pregnant); 1007D; 7 days; Control animals received mp w/ vehicle; animal info (C57BL/6, female, 2, 10, 18 mo old); ALZET brain infusion kit 3 used.
Q2021 Karimi-Abdolrezaee,S., Schut,D., Wang,J., Fehlings,M.G. Chondroitinase and Growth Factors Enhance Activation and Oligodendrocyte Differentiation of Endogenous Neural Precursor Cells after Spinal Cord Injury. PLoS One 2012; 7(-5-):U605-U620. >>> Epidermal growth factor; fibroblast growth factor, basic; platelet derived growth factor-AA; Saline; albumin, rat serum; CSF/CNS (intrathecal); Rat; 1007D; 7 days; Controls received mp w/ vehicle; animal info (Wistar, female, 250 g); spinal cord injury; intrathecal catheter used (0007741).
Q1565 Hewitt,S.C., Kissling,G.E., Fieselman,K.E., Jayes,F.L., Gerrish,K.E., Korach,K.S. Biological and biochemical consequences of global deletion of exon 3 from the ER-alpha gene. FASEB Journal 2010; 24(-12-):4660-4667. >>> Epidermal growth factor; Mice; 24 hours; Animal info (Ex3 alpha ERKO).
Q1335 Sun,D., Bullock,M.R., Altememi,N., Zhou,Z.W., Hagood,S., Rolfe,A., McGinn,M.J., Hamm,R., Colello,R.J. The Effect of Epidermal Growth Factor in the Injured Brain after Trauma in Rats. Journal of Neurotrauma 2010; 27(-5-):923-938. >>> Epidermal growth factor, recomb. human; CSF, artificial; CSF/CNS; Rat; 1007D; 7 days; Controls received mp w/ vehicle; animal info (male, 3-4 mo old, Sprague Dawley, 300 g); functionality of mp verified by residual volume; ALZET brain infusion kit 2 used; artificial CSF recipe; cannula placement verified by injecting Evan’s Blue dye into the cannula.
Q1151 Joseph,N.M., He,S.H., Quintana,E., Kim,Y.G., Nunez,G., Morrison,S.J. Enteric glia are multipotent in culture but primarily form glia in the adult rodent gut. Journal of Clinical Investigation 2011; 121(-9-):3398-3411. >>> Epidermal growth factor; fibroblast growth factor; glial-derived neurotrophic factor; BSA; PBS; IP; Rat; 7 days; Controls received mp w/ vehicle; animal info (P90).
Q1055 Erlandsson,A., Lin,C.H.A., Yu,F.G., Morshead,C.M. Immunosuppression promotes endogenous neural stem and progenitor cell migration and tissue regeneration after ischemic injury. Experimental Neurology 2011; 230(-1-):48-57. >>> Epidermal growth factor, recomb. human; erythropoietin; cyclosporine A; CSF/CNS; SC; Mice; 1007D; ; Animal info (male, C57/BL6, 8-10 wks old); pumps replaced after 7 days; ALZET brain infusion kit 3 used.
Q0798 Miksa,M., Wu,R.Q., Dong,W.F., Komura,H., Amin,D., Ji,Y.X., Wang,Z.M., Wang,H.C., Ravikumar,T.S., Tracey,K.J., Wang,P. Immature Dendritic Cell-Derived Exosomes Rescue Septic Animals Via Milk Fat Globule Epidermal Growth Factor VIII. Journal of Immunology 2009; 183(-9-):5983-5990. >>> Epidermal growth factor VIII, milk fat globule, recomb. murine; IV (jugular); Rat; 2001D; 20 hours; Controls received mp w/ PBS; immunology; animal info (male, Sprague-Dawley).
Q0793 Gonzalez-Perez,O., Romero-Rodriguez,R., Soriano-Navarro,M., Garcia-Verdugo,J.M., varez-Buylla,A. Epidermal Growth Factor Induces the Progeny of Subventricular Zone Type B Cells to Migrate and Differentiate into Oligodendrocytes. Stem Cells 2009; 27(-8-):2032-2043. >>> Epidermal growth factor; BSA; saline; CSF/CNS; Mice; 1007D; 7 days; Controls received mp w/ vehicle; animal info (adult, CD-1); schematic of pump and cannula placement, figure 4.
Q0699 Gampe,K., Brill,M.S., Momma,S., Goetz,M., Zimmermann,H. EGF induces CREB and ERK activation at the wall of the mouse lateral ventricles. Brain Research 2011; 1376(-;-):31-41. >>> Epidermal growth factor, recomb.; CSF, artificial; CSF/CNS; Mice; 1007D; 6 days; Controls received mp w/ vehicle; animal info (,ale, C57BL/6N, 8-10 wks old); artificial CSF formula.
Q0397 Aguirre,A., Rubio,M.E., Gallo,V. Notch and EGFR pathway interaction regulates neural stem cell number and self-renewal. Nature 2010; 467(-7313-):323-U101. >>> Ara-C; epidermal growth factor; Saline; CSF/CNS (surface); CSF/CNS; Mice; 5, 6 days; Controls received mp w/vehicle; animal info (Cnp-hEGFR); incorrectly stated model 1007.
Q0248 Kolb,B, Morshead,C., Gonzalez,C., Kim,M., Gregg,C., Shingo,T., Weiss,S. Growth factor-stimulated generation of new cortical tissue and functional recovery after stroke damage to the motor cortex of rats. Journal of Cerebral Blood Flow and Metabolism 2007; 27(–):983-997. >>> Erythropoietin; epidermal growth factor; CSF, artificial; CSF/CNS; Rat; 2001; 7, 14 days; Controls received mp w/ vehicle; peptides; animal info (male, Long-Evans, 90-110 days old); ischemia (cerebral); behavioral testing (forelimb assymetry, forelimb inhibition (swimming), reaching); some animals received 7 days EGF.
Q0241 Im,S.H., Yu,J.H., Park,E.S., Lee,J.E., Kim,H.O., Park,K.I., Kim,G.W., Park,C.I., Cho,S.R. INDUCTION OF STRIATAL NEUROGENESIS ENHANCES FUNCTIONAL RECOVERY IN AN ADULT ANIMAL MODEL OF NEONATAL HYPOXIC-ISCHEMIC BRAIN INJURY. Neuroscience 2010; 169(-1-):259-268. >>> Brain-derived neurotrophic factor; epidermal growth factor; ara-C; CSF/CNS; Mice; 1002; 2 weeks; Controls received mp w/ PBS; ALZET brain infusion kit 3 used; animal info (ICR, 6 wks old); behavioral testing (rotarod performance, forelimb-use asymmetry test).
Q0061 Karimi-Abdolrezaee,S., Eftekharpour,E., Wang,J., Schut,D., Fehlings,M.G. Synergistic Effects of Transplanted Adult Neural Stem/Progenitor Cells, Chondroitinase, and Growth Factors Promote Functional Repair and Plasticity of the Chronically Injured Spinal Cord. Journal of Neuroscience 2010; 30(-5-):1657-1676. >>> Chondroitinase ABC; epidermal growth factor; fibroblast growth factor; platelet-derived growth factor; Penicillinase; saline; albumin, rat serum; CSF, artificial; gentamicin; BSA; CSF/CNS (intrathecal, subarachnoid space); Rat; 1007D; 7 days; Controls received mp w/ vehicle; animal info (female, Wistar, 250 g.); ALZET intrathecal catheter used (0007741).
P9944 Agrawal,A., Min,D.H., Singh,N., Zhu,H.H., Birjiniuk,A., von Maltzahn,G., Harris,T.J., Xing,D.Y., Woolfenden,S.D., Sharp,P.A., Charest,A., Bhatia,S. Functional Delivery of siRNA in Mice Using Dendriworms. ACS Nano 2009; 3(-9-):2495-2504. >>> RNA, small interfering; epidermal growth factor receptor; dendriworm, dye-labeled; RNA, small interfering, GFP, dendriworm, dye-labeled; CSF/CNS (intratumoral); Mice; 3, 7 days; Tissue perfusion (tumor); cancer (glioblastoma); incorrectly stated pump model 2007; Plastics One cannula used; animial info (Swiss Webster).
P9843 Oya,S., Yoshikawa,G., Takai,K., Tanaka,J.I., Higashiyama,S., Saito,N., Kirino,T., Kawahara,N. ATTENUATION OF Notch SIGNALING PROMOTES THE DIFFERENTIATION OF NEURAL PROGENITORS INTO NEURONS IN THE HIPPOCAMPAL CA1 REGION AFTER ISCHEMIC INJURY. Neuroscience 2009; 158(-2-):683-692. >>> Epidermal growth factor, recomb. human; fibroblast growth factor, recomb. human; Jag1, recomb. rat; S2188; DLL4, recomb. mouse; CSF, artificial, DMSO; CSF/CNS; Rat; 1003D; 1007D; 11 days; Controls received mp w/ vehicle; pumps replaced after 3 days; enzyme inhibitor (gamma secretase); animal info (male, Wistar, adult, 8 wks old, 280-320 g.); ischemia (cerebral); bilateral infusion; 10% DMSO used; brain tissue distribution.
P9520 Thatch,K.A., Schwartz,M.Z., Yoo,E.Y., Mendelson,K.G., Duke,D.S. Modulation of the inflammatory response and apoptosis using epidermal growth factor and hepatocyte growth factor in a liver injury model: a potential approach to the management and treatment of cholestatic liver disease. Journal of Pediatric Surgery 2008; 43(-12-):2169-2173. >>> Epidermal growth factor, recomb. human; human growth factor, recomb. human; IV; Rat; 7 days; Controls received mp w/ PBS; animal info (female, adult, Sprague Dawley, 200-250 g.).
P9320 De Toni,A., Zbinden,M., Epstein,J.A., Altaba,A.R.I., Prochiantz,A., Caille,I. Regulation of survival in adult hippocampal and glioblastoma stem cell lineages by the homeodomain-only protein HOP. Neural Development 2008; 3(-;-):U2-U13. >>> Epidermal growth factor; fibroblast growth factor, basic; RNA, small interfering; Saline, physiological; CSF/CNS; CSF/CNS (dentate gyrus); Rat; 1003D; 3 days; Controls received mp w/ control siRNA; cancer (glioblastoma); peptides; animal info (Swiss, HOP -/-, wt, adult); HOP or control siRNA was coupled to the cell permeant peptide, penetratin.
P8932 Oya,S., Yoshikawa,G., Takai,K., Tanaka,J.I., Higashiyama,S., Saito,N., Kirino,T., Kawahara,N. Region-specific proliferative response of neural progenitors to exogenous stimulation by growth factors following ischemia. NeuroReport 2008; 19(-8-):805-810. >>> Epidermal growth factor, recomb. human; fibroblast growth factor-2, recomb. human; insulin-like growth factor I, recomb. human; erythropoietin, recomb. rat; brain-derived neurotrophic factor, recomb. human; DDL4, recomb. mouse; CSF/CNS; Rat; 1003D; 3 days; Ischemia; animal info (male, Wistar, 8wks old, 280-300 g.); bilateral infusion.
P8794 Louis,S.A., Rietze,R.L., Deleyrolle,L., Wagey,R.E., Thomas,T.E., Eaves,A.C., Reynolds,B.A. Enumeration of neural stem and progenitor cells in the neural colony-forming cell assay. Stem Cells 2008; 26(-4-):988-996. >>> Epidermal growth factor; ara-c; Saline; CSF/CNS; Mice; 1007D; 7 days; Controls received mp w/ vehicle; cyanoacrylate adhesive; animal info (adult, C57BL/6).
P8705 Mizuno,M., Sotoyama,H., Narita,E., Kawamura,H., Namba,H., Zheng,Y.J., Eda,T., Nawa,H. A cyclooxygenase-2 inhibitor ameliorates behavioral impairments induced by striatal administration of epidermal growth factor. Journal of Neuroscience 2007; 27(-38-):10116-10127. >>> Epidermal growth factor, recomb. human; Saline; CSF/CNS (striatum); CSF/CNS (nucleus accumbens); Rat; 2002; 8-14 days; Controls received mp w/ vehicle; functionality of mp verified by residual volume; dose-response (fig. 1); peptides; multiple pumps per animal (2); post op. care (cefmetazon); animal info (male, Sprague-Dawley, 7-8 wks old, 300-380g); cannula position confirmed after completion of tests.
P8632 Han,G.P., Li,L., Kosugi,I., Kawasaki,H., Tsuchida,T., Miura,K., Tsutsui,Y. Enhancement of susceptibility of adult mouse brain to cytomegalovirus infection by infusion of epidermal growth factor. Journal of Neuroscience Research 2007; 85(-13-):2981-2990. >>> Epidermal growth factor, mouse; PBS; CSF/CNS; Mice; 1003D; 3 days; Controls received mp w/ vehicle; peptides; animal info (female, BALB/c; 10, 25, and 70 wks old).
2. Fibroblast Growth Factor
Q2719 Hawryluk,G.W.J., Mothe,A., Wang,J., Wang,S., Tator,C., Fehlings,M.G. An In Vivo Characterization of Trophic Factor Production Following Neural Precursor Cell or Bone Marrow Stromal Cell Transplantation for Spinal Cord Injury. STEM CELLS AND DEVELOPMENT 2012; 21(-12-):2222-2238. >>> Epidermal growth factor; fibroblast growth factor, beta; platelet-derived growth factor, alpha; CSF/CNS (intrathecal); Rat; 1007D; 7 days; Animal info (adult, female, tg).
Q2655 Kharitonenkov,A., Beals,J.M., Micanovic,R., Strifler,B.A., Rathnachalam,R., Wroblewski,V.J., Li,S., Koester,A., Ford,A.M., Coskun,T., Dunbar,J.D., Cheng,C.C., Frye,C.C., Bumol,T.F., Moller,D.E. Rational Design of a Fibroblast Growth Factor 21-Based Clinical Candidate, LY2405319. PLoS One 2013; 8(-3-):U650-U659. >>> Fibroblast growth factor-21; SC; Mice; 7, 14 days; Control animals received mp w/ vehicle; animal info (18 wks old, DIO, C57BL/6).
Q2645 Adams,A.C., Cheng,C.C., Coskun,T., Kharitonenkov,A. FGF21 Requires betaklotho to Act In Vivo. PLoS One 2012; 7(-11-):U405-U412. >>> Fibroblast growth factor-21; Mice; 14 days; Animal info (male, wt, KLBKO).
Q2480 Murphy,M., Samms,R., Warner,A., Bolborea,M., Barrett,P., Fowler,M.J., Brameld,J.M., Tsintzas,K., Kharitonenkov,A., Adams,A.C., Coskun,T., Ebling,F.J.P. Increased Responses to the Actions of Fibroblast Growth Factor 21 on Energy Balance and Body Weight in a Seasonal Model of Adiposity. Journal of Neuroendocrinology 2013; 25(-2-):180-189. >>> Fibroblast growth factor-21, recomb. human; Saline; SC; Hamster; 2002; 14 days; Control animals received mp w/ vehicle; animal info (adult, male); post op. care (Rimadyl).
Q2417 Sleeman,I.J., Boshoff,E.L., Duty,S. Fibroblast growth factor-20 protects against dopamine neuron loss in vitro and provides functional protection in the 6-hydroxydopamine-lesioned rat model of Parkinson’s disease. Neuropharmacology 2012; 63(-7-):1268-1277. >>> Fibroblast growth factor-20; Serum free medium; rat serum albumin; CSF/CNS (supra-nigra); Rat; 1007D; 6 days; Control animals received mp w/ vehicle; animal info (Sprague Dawley, male, 250-300 g); cyanoacrylate used; neurodegenerative (Parkinson’s disease).
Q2411 Huang,W.H., Li,Y.D., Lin,Y.F., Ye,X., Zang,D.W. Effects of leukemia inhibitory factor and basic fibroblast growth factor on free radicals and endogenous stem cell proliferation in a mouse model of cerebral infarction. Neural Regeneration Research 2012; 7(-19-):1469-1474. >>> Leukemia inhibitory factor; fibroblast growth factor, basic; Saline, normal; Mice; 21 days; Animal info (C57BL/6, male, 8 wks old).
Q2021 Karimi-Abdolrezaee,S., Schut,D., Wang,J., Fehlings,M.G. Chondroitinase and Growth Factors Enhance Activation and Oligodendrocyte Differentiation of Endogenous Neural Precursor Cells after Spinal Cord Injury. PLoS One 2012; 7(-5-):U605-U620. >>> Epidermal growth factor; fibroblast growth factor, basic; platelet derived growth factor-AA; Saline; albumin, rat serum; CSF/CNS (intrathecal); Rat; 1007D; 7 days; Controls received mp w/ vehicle; animal info (Wistar, female, 250 g); spinal cord injury; intrathecal catheter used (0007741).
Q2020 Adams,A.C., Coskun,T., Rovira,A.R.I., Schneider,M.A., Raches,D.W., Micanovic,R., Bina,H.A., Dunbar,J.D., Kharitonenkov,A. Fundamentals of FGF19&FGF21 Action In Vitro and In Vivo. PLoS One 2012; 7(-5-):U1479-U1489. >>> Fibroblast growth factor 19; fibroblast growth factor 21; uridine, bromodeoxy; PBS; SC; Mice; 7 days; Controls received mp w/ vehicle; animal info (male, C57BL/6J, ob/ob, 9 wks old); labeling of hepatocytes.
Q1884 Jang,E., Albadawi,H., Watkins,M.T., Edelman,E.R., Baker,A.B. Syndecan-4 proteoliposomes enhance fibroblast growth factor-2 (FGF-2)-induced proliferation, migration, and neovascularization of ischemic muscle. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2012; 109(-5-):1679-1684. >>> Fibroblast growth factor-2; syndecan-4, proteoliposome; SC; Rat; 1004; 7-16 days; Controls received mp w/ PBS; animal info (Sprague Dawley); wound clips used; ischemia.
Q1741 Frontini,M.J., Nong,Z.X., Gros,R., Drangova,M., O’Neil,C., Rahman,M.N., Akawi,O., Yin,H., Ellis,C.G., Pickering,J.G. Fibroblast growth factor 9 delivery during angiogenesis produces durable, vasoresponsive microvessels wrapped by smooth muscle cells. NATURE BIOTECHNOLOGY 2011; 29(-5-):421-U232. >>> Fibroblast growth factor-9; PBS; IA (femoral); Mice; 1007D; ; Controls received mp w/ vehicle; animal info (male, C57BL/6J, 9-10 mo old); polyethylene tubing used; ischemia (hind limb).
Q1677 Wu,A.L., Kolumam,G., Stawicki,S., Chen,Y.M., Li,J., Zavala-Solorio,J., Phamluong,K., Feng,B., Li,L., Marsters,S., Kates,L., van Bruggen,N., Leabman,M., Wong,A., West,D., Stern,H., Luis,E., Kim,H.S., Yansura,D., Peterson,A.S., Filvaroff,E., Wu,Y., Sonoda,J. Amelioration of Type 2 Diabetes by Antibody-Mediated Activation of Fibroblast Growth Factor Receptor 1. Science Translational Medicine 2011; 3(-113-):U32-U41. >>> Fibroblast growth factor 21, recomb. human; PBS; SC; Mice; 2001; ; Controls received mp w/ vehicle; animal info (adult, male, female, C57BL/6J, db/db).
Q1567 Yoshikawa,G., Momiyama,T., Oya,S., Takai,K., Tanaka,J.I., Higashiyama,S., Saito,N., Kirino,T., Kawahara,N. Induction of striatal neurogenesis and generation of region-specific functional mature neurons after ischemia by growth factors Laboratory investigation. Journal of Neurosurgery 2010; 113(-4-):835-850. >>> Fibroblast growth factor-2; CSF, artificial; albumin, rat serum; CSF/CNS; Rat; 1007D; 7 days; Controls received mp w/ vehicle; animal info (Wistar, male, 8-10 wks old, 280-320 g); bilateral infusion.
Q1404 Wu,A.L., Coulter,S., Liddle,C., Wong,A.N., Eastham-Anderson,J., French,D.M., Peterson,A.S., Sonoda,J. FGF19 Regulates Cell Proliferation, Glucose and Bile Acid Metabolism via FGFR4-Dependent and Independent Pathways. PLoS One 2011; 6(-3-):U433-U443. >>> Fibroblast growth factor 19; FGF19v; SC; Mice; 2001; 7 days; Controls received mp w/ vehicle; animal info (ob/ob, C57BL/6, 11 wks old, 12-15 wks old, Fgfr wt); FGF19v is a fibroblast growth factor variant.
Q1362 Toledo,R.N., Borin,A., Cruz,O.L.M., Ho,P.L., Testa,J.R.G., Fukuda,Y. The Action of Topical Basic Fibroblast Growth Factor in Facial Nerve Regeneration. OTOLOGY&NEUROTOLOGY 2010; 31(-3-):498-505. >>> Fibroblast growth factor, basic; albumin, human; Ringer lactate solution; CSF/CNS (facial nerve anastomosis); Rat; 2002; 14 days; Controls received mp w/ sodium heparin, human albumin in Ringer lactate solution; animal info (male, Wistar, adult); functionality of mp verified by residual volume; good methods, pg 499; stress/adverse reaction: (see pg. 501) “neuroma at the anastomosis”, “hemoatoma at the surgical incision”; tissue perfusion (epineural anastomosis); vinyl catheter used; “We chose to use minipumps because this method allows better control of the quantity of bFGF delivered at the target site and is compatible with standard facial nerve surgical techniques. Furthermore, the isolate reservoir of the minipumps prevents the contact of the study drug with substances that could inactivate it” pg 502.
Q1236 Miyasaka,E.A., Raghavan,S., Gilmont,R.R., Mittal,K., Somara,S., Bitar,K.N., Teitelbaum,D.H. In vivo growth of a bioengineered internal anal sphincter: comparison of growth factors for optimization of growth and survival. PEDIATRIC SURGERY INTERNATIONAL 2011; 27(-2-):137-143. >>> Fibroblast growth factor-2; vascular endothelial growth factor-2; platelet-derived growth factor; SC; Mice; 1004; 28 days; Controls received mp with no growth factors; animal info (C57BL/6); good methods, pg 138; tissue perfusion (internal anal sphincter); silicone catheter used; “the osmotic pumps we used completed delivery of the growth factors by 28 days, which would clearly limit the duration of exposure to the growth factor, lessening the risk of malignancy” pg 143.
Q1151 Joseph,N.M., He,S.H., Quintana,E., Kim,Y.G., Nunez,G., Morrison,S.J. Enteric glia are multipotent in culture but primarily form glia in the adult rodent gut. Journal of Clinical Investigation 2011; 121(-9-):3398-3411. >>> Epidermal growth factor; fibroblast growth factor; glial-derived neurotrophic factor; BSA; PBS; IP; Rat; 7 days; Controls received mp w/ vehicle; animal info (P90).
Q0891 MacMillan,K.S., Naidoo,J., Liang,J., Melito,L., Williams,N.S., Morlock,L., Huntington,P.J., Estill,S.J., Longgood,J., Becker,G.L., McKnight,S.L., Pieper,A.A., De Brabander,J.K., Ready,J.M. Development of Proneurogenic, Neuroprotective Small Molecules. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 2011; 133(-5-):1428-1437. >>> P7C3; analogue, P7C3; fibroblast growth factor-2; DMSO; cremophor EL; dextrose; water; CSF/CNS; Mice; 1007D; 7 days; Positive controls received mp w/ FGF-2; animal info (12 week old, C57BL/J6); neurodegenerative (Alzheimer’s disease); 3% DMSO used.
Q0482 Theurl,M., Schgoer,W., Albrecht,K., Jeschke,J., Egger,M., Beer,A.G.E., Vasiljevic,D., Rong,S., Wolf,A.M., Bahlmann,F.H., Patsch,J.R., Wolf,D., Schratzberger,P., Mahata,S.K., Kirchmair,R. The Neuropeptide Catestatin Acts As a Novel Angiogenic Cytokine via a Basic Fibroblast Growth Factor-Dependent Mechanism. Circulation Research 2010; 107(-11-):1326-1U95. >>> Antibody, fibroblast growth factor, b-, mouse; SC; Mice; 3, 4 weeks; Controls received mp w/control antibody; animal info (male, C57BL/6 wild-type, 12-15 mo old).
Q0308 Raghavan,S., Miyasaka,E.A., Hashish,M., Somara,S., Gilmont,R.R., Teitelbaum,D.H., Bitar,K.N. Successful implantation of physiologically functional bioengineered mouse internal anal sphincter. American Journal of Physiology-Gastrointestinal and Liver Physiology 2010; 299(-2-):G430-G439. >>> Fibroblast growth factor-2, human, recomb; SC; Mice; 1004; 21 days; Animal info (C57BL/6J female, specific pathogen-free, 8 wk old); ALZET PE catheter used; catheter connected to physiologically functional bioengineered mouse internal anal sphincter; tissue perfusion (internal anal sphincter).
Q0106 Sarruf,D.A., Thaler,J.P., Morton,G.J., German,J., Fischer,J.D., Ogimoto,K., Schwartz,M.W. Fibroblast Growth Factor 21 Action in the Brain Increases Energy Expenditure and Insulin Sensitivity in Obese Rats. Diabetes 2010; 59(-7-):1817-1824. >>> Fibroblast growth factor-21, recomb. human; BSA; CSF/CNS; Rat; 2002; 2 weeks; Controls received mp w/ vehicle; ALZET brain infusion kit 2 used; animal info (male, Wistar, 250-275 g); Research diets D12492; diabetes.
Q0063 Hashish,M., Raghavan,S., Somara,S., Gilmont,R.R., Miyasaka,E., Bitar,K.N., Teitelbaum,D.H. Surgical implantation of a bioengineered internal anal sphincter. Journal of Pediatric Surgery 2010; 45(-1-):52-58. >>> Fibroblast growth factor-2, recomb.; PBS, sterile; SC; Mice; 1004; 25 days; Controls received mp w/ vehicle; tissue perfusion (internal anal sphincter); no stress (see pg. 57); good methods (pg. 53); animal info (female, C57BL/6, 8 wks old); “use of such pumps provided constant infusion over the postimplantation period without observed evidence of systemic effects and allowed increased efficiency of the drug owing to its proximity” pg. 57; operative photographs (pg. 54).
Q0061 Karimi-Abdolrezaee,S., Eftekharpour,E., Wang,J., Schut,D., Fehlings,M.G. Synergistic Effects of Transplanted Adult Neural Stem/Progenitor Cells, Chondroitinase, and Growth Factors Promote Functional Repair and Plasticity of the Chronically Injured Spinal Cord. Journal of Neuroscience 2010; 30(-5-):1657-1676. >>> Chondroitinase ABC; epidermal growth factor; fibroblast growth factor; platelet-derived growth factor; Penicillinase; saline; albumin, rat serum; CSF, artificial; gentamicin; BSA; CSF/CNS (intrathecal, subarachnoid space); Rat; 1007D; 7 days; Controls received mp w/ vehicle; animal info (female, Wistar, 250 g.); ALZET intrathecal catheter used (0007741).
P9843 Oya,S., Yoshikawa,G., Takai,K., Tanaka,J.I., Higashiyama,S., Saito,N., Kirino,T., Kawahara,N. ATTENUATION OF Notch SIGNALING PROMOTES THE DIFFERENTIATION OF NEURAL PROGENITORS INTO NEURONS IN THE HIPPOCAMPAL CA1 REGION AFTER ISCHEMIC INJURY. Neuroscience 2009; 158(-2-):683-692. >>> Epidermal growth factor, recomb. human; fibroblast growth factor, recomb. human; Jag1, recomb. rat; S2188; DLL4, recomb. mouse; CSF, artificial, DMSO; CSF/CNS; Rat; 1003D; 1007D; 11 days; Controls received mp w/ vehicle; pumps replaced after 3 days; enzyme inhibitor (gamma secretase); animal info (male, Wistar, adult, 8 wks old, 280-320 g.); ischemia (cerebral); bilateral infusion; 10% DMSO used; brain tissue distribution.
P9669 Sun,D, Bullock,M.R., McGinn,M.J., Zhou,Z., Altememi,N., Hagood,S., Hamm,R, Colello,R.J. Basic fibroblast growth factor-enhanced neurogenesis contributes to cognitive recovery in rats following traumatic brain injury. Experimental Neurology 2009; 216(-1-):56-65. >>> Fibroblast growth factor, b- recomb. human; CSF, artificial; CSF/CNS; Rat; 1007D; 7 days; Controls received mp w/ vehicle; ALZET brain infusion kit 2 used; animal info (male, Sprague Dawley, 3 months old, 300 g.).
P9320 De Toni,A., Zbinden,M., Epstein,J.A., Altaba,A.R.I., Prochiantz,A., Caille,I. Regulation of survival in adult hippocampal and glioblastoma stem cell lineages by the homeodomain-only protein HOP. Neural Development 2008; 3(-;-):U2-U13. >>> Epidermal growth factor; fibroblast growth factor, basic; RNA, small interfering; Saline, physiological; CSF/CNS; CSF/CNS (dentate gyrus); Rat; 1003D; 3 days; Controls received mp w/ control siRNA; cancer (glioblastoma); peptides; animal info (Swiss, HOP -/-, wt, adult); HOP or control siRNA was coupled to the cell permeant peptide, penetratin.
P9296 Zhao,H.D., Negash,L., Wei,Q., LaCour,T.G., Estill,S.J., Capota,E., Pieper,A.A., Harran,P.G. Acid promoted cinnamyl ion mobility within peptide derived macrocycles. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 2008; 130(-42-):13864-13866. >>> Fibroblast growth factor, recomb.; peptides, synthetic; cyclophane 17, meta-; CSF, artificial; CSF/CNS; Mice; 7 days; Controls received mp w/ vehicle or FGF; dose-response (fig. 3); animal info (adult, C57BL/6J); peptides.
P9180 Coskun,T., Bina,H.A., Schneider,M.A., Dunbar,J.D., Hu,C.C., Chen,Y.Y., Moller,D.E., Kharitonenkov,A. Fibroblast Growth Factor 21 Corrects Obesity in Mice. Endocrinology 2008; 149(-12-):6018-6027. >>> Fibroblast growth factor 21; SC; Mice; 2 weeks; Comparison of SC injections vs. mp; half-life (p. 6025) 1 hour in mice; peptides; animal info (male, DIO, ob/ob, C57BL/6); obesity; “approximately a 10-fold greater dose of FGF21 was required to achieve an equivalent weight reduction compared with FGF21 administration via ALZET pumps.” pg. 6021.
P8932 Oya,S., Yoshikawa,G., Takai,K., Tanaka,J.I., Higashiyama,S., Saito,N., Kirino,T., Kawahara,N. Region-specific proliferative response of neural progenitors to exogenous stimulation by growth factors following ischemia. NeuroReport 2008; 19(-8-):805-810. >>> Epidermal growth factor, recomb. human; fibroblast growth factor-2, recomb. human; insulin-like growth factor I, recomb. human; erythropoietin, recomb. rat; brain-derived neurotrophic factor, recomb. human; DDL4, recomb. mouse; CSF/CNS; Rat; 1003D; 3 days; Ischemia; animal info (male, Wistar, 8wks old, 280-300 g.); bilateral infusion.
P8930 Abbaspour,A., Takata,S., Sairyo,K., Katoh,S., Yukata,K., Yasul,N. Continuous local infusion of fibroblast growth factor-2 enhances consolidation of the bone segment lengthened by distraction osteogenesis in rabbit experiment. Bone 2008; 42(-1-):98-106. >>> Fibroblast growth factor-2, recomb. human; Bone (tibia); Rabbit; 2ML4; 14 days; half-life (p. 104) “relatively short”; tissue perfusion (tibia); animal info (male, 1.8-2.2 kg., osteotomized); polyvinyl catheter tubing used; pump image fig. 1e.
P8818 Conigliaro,A., Colletti,M., Cicchini,C., Guerra,M.T., Manfredini,R., Zini,R., Bordoni,V., Siepi,F., Leopizzi,M., Tripodi,M., Amicone,L. Isolation and characterization of a murine resident liver stem cell. CELL DEATH AND DIFFERENTIATION 2008; 15(-1-):123-133. >>> Fibroblast growth factor, bovine; Heparin; SC; Mice (nude); 10 days; Peptides.
P8702 Grumbles,R.M., Casella,G.T.B., Rudinsky,M.J., Wood,P.M., Sesodia,S., Bent,M., Thomas,C.K. Long-term delivery of FGF-6 changes the fiber type and fatigability of muscle reinnervated from embryonic neurons transplanted into adult rat peripheral nerve. Journal of Neuroscience Research 2007; 85(-9-):1933-1942. >>> Fibroblast growth factor-6, recomb. human; PBS; BSA; IM (medial gastrocnemius); Rat; 2ML4; 4 weeks; Controls received mp w/ vehicle; peptides; animal info (female, Fischer, adult).
P8661 Miller,J.M., Le Prell,C.G., Prieskorn,D.M., Wys,N.L., Altschuler,R.A. Delayed neurotrophin treatment following deafness rescues spiral ganglion cells from death and promotes regrowth of auditory nerve peripheral processes: Effects of brain-derived neurotrophic factor and fibroblast growth factor. Journal of Neuroscience Research 2007; 85(-9-):1959-1969. >>> Brain-derived neurotrophic factor; fibroblast growth factor-1; Perilymph, artificial; albumin, guinea pig serum; Ear (scala tympani); Guinea-pig; 2002; 26 days; Controls received mp w/ vehicle; pumps replaced at day 13; peptides; tissue perfusion (scala tympani); animal info (male, female, pigmented, 250-300g, deafened).
P8658 Rai,K.S., Hattiangady,B., Shetty,A.K. Enhanced production and dendritic growth of new dentate granule cells in the middle-aged hippocampus following intracerebroventricular FGF-2 infusions. European Journal of Neuroscience 2007; 26(-7-):1765-1779. >>> Fibroblast growth factor-2; CSF, artificial; CSF/CNS; Rat; 2002; 14 days; Controls received mp w/ vehicle; functionality of mp verified by residual volume; good methods (p. 1766-1767); ALZET brain infusion kit used; cyanoacrylate adhesive; post op. care (tetracycline); animal info (male, F344, 12 months).
P8631 Powell,JA Jr, Mousa,S.A. Neutrophil-Activating Protein-2- and Interieukin-8-Mediated Angiogenesis. Journal of Cellular Biochemistry 2007; 102(-2-):412-420. >>> Fibroblast growth factor-2, basic, human; penicillamine, S-nitroso N-acetyl; glutathione, S-nitroso N-acetyl; SC; Mice; 14 days; Peptides; animal info (male, C57BL/6, 6-8 wks old); SNAP and SNAG are nitric oxide donors.
P8478 Ma,T., Gutnick,J., Salazar,B., Larsen,M.D., Suenaga,E., Zilber,S., Huang,Z., Huddleston,J., Smith,R.L., Goodman,S. Modulation of allograft incorporation by growth factors over a prolonged continuous infusion of duration in vivo. Bone 2007; 41(-3-):386-392. >>> Fibroblast growth factor-2; osteogenic protein-1, recomb. human; Water, distilled; acetate buffer; Bone (tibia); Rabbit; 2004; 4,36 weeks; Controls received no treatment to contralateral side; long-term study; pumps replaced every 4 weeks, with 4 week rest periods between 4 week infusion periods; animal info (New Zealand white, 6-12 months old, 3.5-4.2 kg); peptides; OP-1 also known as bone morphogenic protein-7 (BMP-7); tissue perfusion (tibia); unique drug test chamber and bone harvest chamber used in conjunction with mp.
3. Hepatocyte Growth Factor
Q2105 Kitamura,K., Fujiyoshi,K., Yamane,J., Toyota,F., Hikishima,K., Nomura,T., Funakoshi,H., Nakamura,T., Aoki,M., Toyama,Y., Okano,H., Nakamura,M. Human Hepatocyte Growth Factor Promotes Functional Recovery in Primates after Spinal Cord Injury. PLoS One 2011; 6(-11-):U83-U95. >>> Hepatocyte growth factor, recomb. human; PBS; CSF/CNS (intrathecal); Monkey (marmoset); 2004; 4 weeks; Controls received mp w/ vehicle; animal info (adult, female, common, 295-350 g); ALZET rat intrathecal catheter used.
Q1885 Katz,M.S., Thatch,K.A., Schwartz,M.Z. Hepatocyte growth factor and omega-3-enriched feeds have a synergistic effect on mucosal mass in an animal model of inflammatory bowel disease. Journal of Pediatric Surgery 2012; 47(-1-):194-198. >>> Hepatocyte growth factor, human recomb.; PBS; HCL, tris; IV (jugular); Rat; 2002; 14 days; Controls received mp w/ saline; animal info (female, adult, HLA-B27, 200-250 g).
Q1561 Katz,M.S., Thatch,K.A., Schwartz,M.Z. Dose Variation of Hepatocyte Growth Factor and its Effects on an Animal Model of TPN-Induced Liver Injury. Journal of Surgical Research 2010; 163(-2-):294-298. >>> Hepatocyte growth factor; IV (jugular); Rat; 14 days; Controls received mp w/ saline; animal info (Sprague Dawley, female, adult); dose response.
Q0678 Thatch,K.A., Mendelson,K.G., Haber,M.M., Schwartz,M.Z. Growth Factor Manipulation of Intestinal Angiogenesis: A Possible New Paradigm in the Management of Inflammatory Bowel Disease. Journal of Surgical Research 2009; 156(-2-):245-249. >>> Hepatocyte growth factor, recomb. human; HCl, Tris; PBS; IV (jugular); Rat; 1002; 14 days; Controls received mp w/ saline; animal info (female, adult, Fisher).
P9298 Takeo,S., Takagi,N., Takagi,K., Date,I., Ishida,K., Besshoh,S., Nakamura,T., Tanonaka,K. Hepatocyte growth factor suppresses ischemic cerebral edema in rats with microsphere embolism. Neuroscience Letters 2008; 448(-1-):125-129. >>> Hepatocyte growth factor, recomb. human; Saline, physiological; CSF/CNS; Rat; 2001; 3 days; Controls received no treatment; peptides; ischemia (cerebral); animal info (male, Wistar, 220-250 g.).
P9077 Ye,L., Lewis-Russell,J.M., Sanders,A.J., Kynaston,H., Jiang,W.G. HGF/SF up-regulates the expression of bone morphogenetic protein 7 in prostate cancer cells. UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS 2008; 26(-2-):190-197. >>> Hepatocyte growth factor, recomb. human; NK4, recomb. human; SC; Mice (nude); 2004; 4 weeks; Cancer (prostate); animal info (athymic, male, CD-1, 4-6 wks old).
P8927 Chen,J.H., Wu,C.W., Kao,H.L., Chang,H.M., Li,A.F.Y., Liu,T.Y., Chi,C.W. Effects of COX-2 inhibitor on growth of human gastric cancer cells and its relation to hepatocyte growth factor. Cancer Letters 2006; 239(-2-):263-270. >>> Hepatocyte growth factor; IP; Mice (SCID); 28 days; Controls received sham operation; pumps replaced after 14 days; cancer (gastric); peptides; post op. care (streptomycin, penicillin); animal info (male, SCID, 6-8 wks old, 20-25 g.).
P8925 Ye,L., Lewis-Russell,J.M., Davies,G., Sanders,A.J., Kynaston,H., Jiang,W.G. Hepatocyte growth factor up-regulates the expression of the bone morphogenetic protein (BMP) receptors, BMPR-IB and BMPR-II, in human prostate cancer cells. INTERNATIONAL JOURNAL OF ONCOLOGY 2007; 30(-2-):521-529. >>> Hepatocyte growth factor, recomb. human; SC; Mice (nude); 2004; 4 weeks; Controls received mp w/ BSA buffer; cancer (prostate); peptides; animal info (female, athymic, nude, CD-1, 4-6 wks old); HGF antagonist.
P8908 Ishigaki,A., Aoki,M., Nagai,M., Warita,H., Kato,S., Kato,M., Nakamura,T., Funakoshi,H., Itoyama,Y. Intrathecal delivery of hepatocyte growth factor from amyotrophic lateral sclerosis onset suppresses disease progression in rat amyotrophic lateral sclerosis model. Journal of Neuropathology and Experimental Neurology 2007; 66(-11-):1037-1044. >>> Hepatocyte growth factor, recomb. human; PBS, sulfoxide; CSF/CNS (intrathecal, subarachnoid space); Rat (transgenic); 2002; 2004; 2, 4 weeks; Controls received mp w/ vehicle; dose-response (fig. 2); peptides; animal info (G93A Tg, 100 and 115 days old); neurodegenerative (ALS); “we examined the effects of continuous intrathecal delivery of human recombinant HGF (hrHGF) into Tg rats using implanted infusion pumps for selective and less invasive supply of HGF to the spinal cord.” (p.1038).
P8815 Jin,H.K., Yang,R.H., Zheng,Z., Romero,M., Ross,J., Bou-Reslan,H., Carano,R.A.D., Kasman,I., Mai,E., Young,J., Zha,J.P., Zhang,Z.M., Ross,S., Schwall,R., Colbern,G., Merchant,M. MetMAb, the one-armed 5D5 anti-c-Met antibody, inhibits orthotopic pancreatic tumor growth and improves survival. Cancer Research 2008; 68(-11-):4360-4368. >>> Hepatocyte growth factor, human; Dextran sulfate; IP; Mice (nude); 1002; ; Controls received mp w/ vehicle; functionality of mp verified by human HGF serum levels; long-term study; pumps replaced every 12 to 14 days; cancer (pancreatic); peptides; animal info (female, nu/nu).
P8085 Date,I., Takagi,N., Takagi,K., Tanonaka,K., Funakoshi,H., Matsumoto,K., Nakamura,T., Takeo,S. Hepatocyte growth factor attenuates cerebral ischemia-induced increase in permeability of the blood-brain barrier and decreases in expression of tight junctional proteins in cerebral vessels. Neuroscience Letters 2006; 407(-2-):141-145. >>> Hepatocyte growth factor, recomb. human; CSF/CNS; Rat; 2001; 7 days; Controls received mp w/ physiological saline; peptides; ischemia (cerebral); animal info (male, Wistar, 180-220g, microsphere-induced cerebral embolism).
P8009 Niimura,M., Takagi,N., Takagi,K., Mizutani,R., Ishihara,N., Matsumoto,K., Funakoshi,H., Nakamura,T., Takeo,S. Prevention of apoptosis-inducing factor translocation is a possible mechanism for protective effects of hepatocyte growth factor against neuronal cell death in the hippocampus after transient forebrain ischemia. Journal of Cerebral Blood Flow and Metabolism 2006; 26(-11-):1354-1365. >>> Hepatocyte growth factor; Saline; CSF/CNS (right hippocampal region); Rat; 1003D; 3 days; Animal info (male, Wistar, 200-250 grams); ischemia (cerebral); tissue perfusion (hippocampal region).
P8008 Niimura,M., Takagi,N., Takagi,K., Mizutani,R., Tanonaka,K., Funakoshi,H., Matsumoto,K., Nakamura,T., Takeo,S. The protective effect of hepatocyte growth factor against cell death in the hippocampus after transient forebrain ischemia is related to the improvement of apurinic/apyrimidinic endonuclease/redox factor-1 level and inhibition of NADPH oxidase activity. Neuroscience Letters 2006; 407(-2-):136-140. >>> Hepatocyte growth factor; CSF/CNS (right hippocampal region); Rat; 1003D; 3 days; Animal info (male, Wistar, 200-250 grams); ischemia (cerebral); tissue perfusion (hippocampal region).
P7925 Tada,T., Zhan,H., Tanaka,Y., Hongo,K., Matsumoto,K., Nakamura,T. Intraventricular administration of hepatocyte growth factor treats mouse communicating hydrocephalus induced by transforming growth factor beta 1. NEUROBIOLOGY OF DISEASE 2006; 21(-3-):576-586. >>> Hepatocyte growth factor, recomb. human; PBS; BSA; CSF/CNS; Mice; 1007D; 1002; 7,14 days; Animal info (C57BL/6, 10-days old).
P7846 Niimura,M., Takagi,N., Takagi,K., Funakoshi,H., Nakamura,T., Takeo,S. Effects of hepatocyte growth factor on phosphorylation of extracellular signal-regulated kinase and hippocampal cell death in rats with transient forebrain ischemia. European Journal of Pharmacology 2006; 535(-1-3-):114-124. >>> Hepatocyte growth factor, recomb. human; Saline, physiological; CSF/CNS (hippocampus); Rat; 1003D; 1, 2, 3 days; 0.5, 1, 6 hours; Controls received mp w/ vehicle; dose-response (fig. 2); peptides; ischemia (cerebral); animal info (male, Wistar, 200-250g., transient forebrain ischemia by carotid artery occlusion); mp primed in 37 celsius saline.
P7668 Hasuike,S., Ido,A., Uto,H., Moriuchi,A., Tahara,Y., Numata,M., Nagata,K., Hori,T., Hayashi,K., Tsubouchi,H. Hepatocyte growth factor accelerates the proliferation of hepatic oval cells and possibly promotes the differentiation in a 2-acetylaminofluorene/partial hepatectomy model in rats. Journal of Gastroenterology and Hepatology 2005; 20(-11-):1753-1761. >>> Hepatocyte growth factor, recomb. human; PBS; IP; Rat; 7 days; Controls received mp w/ vehicle; functionality of mp verified by human HGF serum levels; replacement therapy (hepatectomy); half-life (pg. 1758)<3 min; animal info (male, Fisher, 8 wk. old).
P7654 Timmapuri,S.J., Otterburn,D.M., Arafat,H., Schwartz,M.Z. Hepatocyte growth factor increases glucagon immunoreactivity in jejunal cells during intestinal adaptation. Journal of Pediatric Surgery 2006; 41(-1-):150-153. >>> Hepatocyte growth factor; IV (jugular); Rat; 2002; 14 days; Controls received mp w/ saline; animal info (male, Sprague-Dawley, adult, 200-225 g); PE catheter used.

4. Insulin-like Growth Factor
Q2675 Secco,M., Bueno,C.Jr, Vieira,N.M., Almeida,C., Pelatti,M., Zucconi,E., Bartolini,P., Vainzof,M., Miyabara,E.H., Okamoto,O.K., Zatz,M. Systemic Delivery of Human Mesenchymal Stromal Cells Combined with IGF-1 Enhances Muscle Functional Recovery in LAMA2 (dy/2j) Dystrophic Mice. Stem Cell Reviews and Reports 2013; 9(-1-):93-109. >>> Insulin-like growth factor-1, R3, long; Acetic acid; SC; Mice; 1002; 8 weeks; Control animals received mp w/ vehicle; animal info (1 mo old, B6.WK-Lama2 dy/2J); long-term study; pumps replaced every 2 weeks.
Q2623 Franco,C., Fernandez,S., Torres-Aleman,I. Frataxin deficiency unveils cell-context dependent actions of insulin-like growth factor I on neurons. Molecular Neurodegeneration 2012; 7(-;-):U1-U10. >>> Insulin-like growth factor-1; SC; Mice; 1 month; Animal info (YG8R, wt, 4-6 mo old).
Q2050 Nishizawa,H., Takahashi,M., Fukuoka,H., Iguchi,G., Kitazawa,R., Takahashi,Y. GH-independent IGF-I action is essential to prevent the development of nonalcoholic steatohepatitis in a GH-deficient rat model. Biochemical and Biophysical Research Communications 2012; 423(-2-):295-300. >>> Growth hormone; insulin-like growth factor I, recomb. human; Saline; SC; Rat; 2004; 4 weeks; Controls received mp w/ vehicle; animal info (SDR, GH-def, male, 16 wks old).
Q1988 Xian,L.L., Wu,X.W., Pang,L.J., Lou,M., Rosen,C.J., Qiu,T., Crane,J., Frassica,F., Zhang,L.M., Rodriguez,J.P., Jia,X.F., Yakar,S., Xuan,S.H., Efstratiadis,A., Wan,M., Cao,X. Matrix IGF-1 maintains bone mass by activation of mTOR in mesenchymal stem cells. Nature Medicine 2012; 18(-7-):1095-U126. >>> Insulin-like growth factor I; insulin-like growth factor binding protein; SC; Mice; 4 weeks; Controls received mp w/ vehicle; animal info (4 wks old, male, LID).
Q1521 Sun,Y., Todd,B.J., Thornton,K., Etgen,A.M., Neal-Perry,G. Differential Effects of Hypothalamic IGF-I on Gonadotropin Releasing Hormone Neuronal Activation During Steroid-Induced LH Surges in Young and Middle-Aged Female Rats. Endocrinology 2011; 152(-11-):4276-4287. >>> JB-1; insulin-like growth factor-1; CSF, artificial; CSF/CNS (third ventricle); Rat; 2002; 7 days; animal info (young , 3-4 mo old, middle-aged, retired breeders, 9-11 mo old, female Sprague Dawley, ovariohysterectomized); guide cannula used; cannula placement verified by tracking the cannula path in brain sections; artificial CSF recipe; peptides;.
Q1506 Sukhanov,S., Higashi,Y., Shai,S.Y., Blackstock,C., Galvez,S., Vaughn,C., Titterington,J., Delafontaine,P. Differential requirement for nitric oxide in IGF-1-induced anti-apoptotic, anti-oxidant and anti-atherosclerotic effects. FEBS Letters 2011; 585(-19-):3065-3072. >>> Insulin-like growth factor-1, recomb. human; Mice; 4, 8, 12 weeks; Controls received mp w/ saline; animal info (Apoe -/-, C57BL/6, 8 wks old); long-term study.
Q1502 Duarte,A.I., Petit,G.H., Ranganathan,S., Li,J.Y., Oliveira,C.R., Brundin,P., Bjoerkqvist,M., Rego,A.C. IGF-1 protects against diabetic features in an in vivo model of Huntington’s disease. Experimental Neurology 2011; 231(-2-):314-319. >>> Insulin-like growth factor-1, recomb. human; Saline; SC; Mice; 1002; 14 days; Controls received mp w/ vehicle; animal info (R6/2, wt, male, 9 wks old); neurodegenerative (Huntington’s disease).
Q1255 Perez-Martin,M., Cifuentes,M., Grondona,J.M., Lopez-Avalos,M.D., Gomez-Pinedo,U., Garcia-Verdugo,J.M., Fernandez-Llebrez,P. IGF-I stimulates neurogenesis in the hypothalamus of adult rats. European Journal of Neuroscience 2010; 31(-9-):1533-1548. >>> Insulin-like growth factor-1; thymidine, H3; CSF/CNS; Rat; 2001; 7 days; Controls received mp w/ saline; animal info (adult, male, Wistar, albino, male, female, 2 mo old); ALZET brain infusion kit used.
Q1232 Menagh,P.J., Turner,R.T., Jump,D.B., Wong,C.P., Lowry,M.B., Yakar,S., Rosen,C.J., Iwaniec,U.T. Growth Hormone Regulates the Balance Between Bone Formation and Bone Marrow Adiposity. Journal of Bone and Mineral Research 2010; 25(-4-):757-768. >>> Insulin-like growth factor 1, recomb. human; SC; Rat; 2001; 5 days; Animal info (female, Sprague-Dawley, HYPOX, 3 mo old).
Q0767 Traub,M.L., De Butte-Smith,M., Zukin,R.S., Etgen,A.M. Oestradiol and Insulin-Like Growth Factor-1 Reduce Cell Loss after Global Ischaemia in Middle-Aged Female Rats. Journal of Neuroendocrinology 2009; 21(-12-):1038-1044. >>> Insulin-like growth factor-I; Saline, sterile; CSF/CNS; Rat; 2004; 28 days; Controls received mp w/ vehicle; animal info (female, Sprague-Dawley, 9-11 mo old, adult, 300-500 g); functionality of mp verified by residual volume; ALZET brain infusion kit used; cannula placement verified by inspection of cryostat sectioning; neuroprotection.
Q0683 Demonbreun,A.R., Fahrenbach,J.P., Deveaux,K., Earley,J.U., Pytel,P., McNally,E.M. Impaired muscle growth and response to insulin-like growth factor 1 in dysferlin-mediated muscular dystrophy. Human Molecular Genetics 2011; 20(-4-):779-789. >>> Insulin-like growth factor-I; 28 days; Controls received mp w/ PBS; animal info (Dysferlin null, wt).
Q0576 Serbedzija,P., Madl,J.E., Ishii,D.N. Insulin and IGF-I prevent brain atrophy and DNA loss in diabetes. Brain Research 2009; 1303(-;-):179-194. >>> Insulin; insulin-like growth factor-I; CSF/CNS; Rat; 12 weeks; Controls received mp w/ aCSF; animal info (Wistar, 275-300 g adult, 9 wks old, male, STZ-induced diabetes); long-term study; pumps replaced at two week intervals; ALZET brain infusion kit used; post op. care (Buprenorphine); cannula placement verified by injecting 20 ul dye through the catheter at time of assay.
Q0466 Cittadini,A., Monti,M.G., Castiello,M.C., D’Arco,E., Galasso,G., Sorriento,D., Saldamarco,L., De Paulis,A., Napoli,R., Iaccarino,G., Sacca,L. Insulin-like growth factor-1 protects from vascular stenosis and accelerates re-endothelialization in a rat model of carotid artery injury. JOURNAL OF THROMBOSIS AND HAEMOSTASIS 2009; 7(-11-):1920-1928. >>> Insulin-like growth factor-1; SC; Rat; ; Controls received mp w/saline; animal info (Sprague-Dawley, male, 210-250 g, ballon injury); 2.0 ul/h rate of infusion.
Q0345 Marino,G., Ugalde,A.P., Fernandez,A.F., Osorio,F.G., Fueyo,A., Freije,J.M.P., Lopez-Otin,C. Insulin-like growth factor 1 treatment extends longevity in a mouse model of human premature aging by restoring somatotroph axis function. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2010; 107(-37-):16268-16273. >>> Insulin-like growth factor-1, human, recomb.; HCl; saline, isotonic, sterile; SC; Mice; 1004; 56 days; Animal info (transgenic, Zmpste24 metalloproteinase deficient); long-term study; pumps replaced after 28 days.
Q0154 Apel,P.J., Ma,J.J., Callahan,M., Northam,C.N., Alton,T.B., Sonntag,W.E., Li,Z.Y. EFFECT OF LOCALLY DELIVERED IGF-1 ON NERVE REGENERATION DURING AGING: AN EXPERIMENTAL STUDY IN RATS. Muscle&Nerve 2010; 41(-3-):335-341. >>> Insulin-like growth factor-I, recomb. human; CSF/CNS (tibial nerve); Rat; 2004; 12 weeks; Controls received mp w/ saline; long-term study; pumps replaced after 6 weeks; animal info (Fischer 344 x Brown Norway, Sprague Dawley; 8 months old, 24 months old); diagram of pump with custom-made T-tube.
Q0153 Moreau,M.L., Sauvant,J., Moos,F., Palin,K. Brain insulin growth factor-I induces diuresis increase through the inhibition of arginin-vasopressin release in aged rats. NEUROBIOLOGY OF AGING 2010; 31(-3-):532-536. >>> Insulin-like growth factor-1, recomb. rat; CSF, artificial; CSF/CNS (third ventricle); Rat; 2ML4; 28 days; Animal info (male, Wistar, 3 months old, 645 g.); guide cannula used; aCSF recipe.
Q0120 Hewitt,S.C., Li,Y., Li,L.P., Korach,K.S. Estrogen-mediated Regulation of Igf1 Transcription and Uterine Growth Involves Direct Binding of Estrogen Receptor-alpha to Estrogen-responsive Elements. Journal of Biological Chemistry 2010; 285(-4-):2676-2685. >>> Insulin-like growth factor-1, synthetic long R3; Acetic acid; saline; IP; Mice; 18, 24 hours; Animal info (female, ERaKO KIKO, wt, 10 weeks old); peptides; replacement therapy (ovariectomy).
Q0078 Todd,B.J., Merhi,Z.O., Shu,J., Etgen,A.M., Neal-Perry,G.S. Hypothalamic Insulin-Like Growth Factor-I Receptors Are Necessary for Hormone-Dependent Luteinizing Hormone Surges: Implications for Female Reproductive Aging. Endocrinology 2010; 151(-3-):1356-1366. >>> JB-1; insulin-like growth factor-1; CSF, artificial; CSF/CNS (third ventricle); Rat; 2002; ; Controls received mp w/ vehicle; animal info (young, 3-4 months old, middle aged, 9-11 months old, adult, female, Sprague Dawley, ovariectomy); Plastics One cannula used; cannula placement verified post mortem by injecting dye into the cannula.
Q0057 Selvamani,A., Sohrabji,F. The Neurotoxic Effects of Estrogen on Ischemic Stroke in Older Female Rats Is Associated with Age-Dependent Loss of Insulin-Like Growth Factor-1. Journal of Neuroscience 2010; 30(-20-):6852-6861. >>> Insulin-like growth factor-1; JB-1; CSF, artificial; CSF/CNS; Rat (pregnant); 1007D; 7 days; Controls received mp w/ vehicle; ALZET brain infusion kit 2 used; cyanoacrylate adhesive; animal info (virgin, 3-4 months old, pregnant, 5-6 months old, retired, 9-11 months old); MCAO.
P9927 Cleveland,B.M., Weber,G.M., Blemings,K.P., Silverstein,J.T. Insulin-like growth factor-I and genetic effects on indexes of protein degradation in response to feed deprivation in rainbow trout (Oncorhynchus mykiss). American Journal of Physiology-Regulatory Integrative and Comparative Physiology 2009; 297(-5-):R1332-R1342. >>> Insulin-like growth factor-1, recomb. human; IP; Fish; 1003D; ; Post op.care (triple antibiotic ointment); animal info (rainbow trout.1 year old); wound clips used.
P9922 Van Mieghem,T., van Bree,R., Van Herck,E., Deprest,J., Verhaeghe,J. Insulin-like growth factor-II regulates maternal hemodynamic adaptation to pregnancy in rats. American Journal of Physiology-Regulatory Integrative and Comparative Physiology 2009; 297(-5-):R1615-R1621. >>> Insulin-like growth factor II, human, recomb.; Saline; SC; Rat (pregnant); 2001; 7 days; Animal info (4 wks old, female, Sprague Dawley).
P9784 Gehrig,S.M., Ryall,J.G., Schertzer,J.D., Lynch,G.S. Insulin-like growth factor-I analogue protects muscles of dystrophic mdx mice from contraction-mediated damage. Experimental Physiology 2008; 93(-11-):1190-1198. >>> Insulin-like growth factor I, LR-; Saline; HCl; SC; Mice; 1004; 4 weeks; Controls received mp w/ vehicle; functionality of mp verified by residual volume; animal info (male, BL/10, mdx, dystrophic, 8-10 wks old).
P9701 Duman,C.H., Schlesinger,L., Terwilliger,R., Russell,D.S., Newton,S.S., Duman,R.S. Peripheral insulin-like growth factor-I produces antidepressant-like behavior and contributes to the effect of exercise. Behavioural Brain Research 2009; 198(-2-):366-371. >>> Insulin-like growth factor I, recomb. human; antibody, anti-IGF-I, polyclonal; Saline; SC; Mice; 1002; 2004; 14, 28 days; Controls received mp w/vehicle; animal info (male, C57BL/6, 10 wks old); behavioral testing (running wheel test, forced swim test).
P9605 Fan,Y., Menon,R.K., Cohen,P., Hwang,D., Clemens,T., DiGirolamo,D.J., Kopchick,J.J., Le Roith,D., Trucco,M., Sperling,M.A. Liver-specific Deletion of the Growth Hormone Receptor Reveals Essential Role of Growth Hormone Signaling in Hepatic Lipid Metabolism. Journal of Biological Chemistry 2009; 284(-30-):19937-19944. >>> Insulin-like growth factor I, recomb. human; SC; Mice; 2 weeks; Controls received mp/placebo; animal info (16 wks old, male, GHRLD).
P9506 Fowlkes,JL. Effects of systemic and local administration of recombinant human IGF-I (rhIGF-I) on de novo bone formation in an aged mouse model. Journal of Bone and Mineral Research 2006; 21(-9-):1359-1366. >>> Insulin-like growth factor I, recomb. human; dye, methylene blue; PBS; SC; bone (tibia); bone (fibula); Mice; 1002; 14 days; Controls received mp w/ vehicle; functionality of mp verified by rhIGF-I serum levels; replacement therapy (mid-diaphyseal osteotomy (tibia, fibula)); peptides; post op. care (buprenex); tissue perfusion (tibia, fibula); animal info (male, C57BL/6, 18 months old).
P9251 Rosendahl,A.H., Holly,J.M.P., Celander,M., Forsberg,G. Systemic IGF-I administration stimulates the in vivo growth of early, but not advanced, renal cell carcinoma. International Journal of Cancer 2008; 123(-6-):1286-1291. >>> Insulin-like growth factor I, recomb. human; Saline, sterile; albumin, mouse serum; SC; Mice (SCID); 1007D; 14 days; Controls received mp w/ vehicle; cancer (renal carcinoma); peptides; animal info (female, SCID CoB-17, 8-12 wks old, 20 g.).
P9141 Seigel,G.M., Lupien,S.B., Campbell,L.A., Ishii,D.N. Systemic IGF-I treatment inhibits cell death in diabetic rat retina. Journal of Diabetes and Its Complications 2006; 20(-3-):196-204. >>> Insulin-like growth factor I; streptozotocin; Acetate; SC; Rat; 2002; 8 weeks; Controls received mp w/ vehicle; long-term study; animal info (Wistar, 12 wks old); diabetes.
P9112 Chu,Y.W., Schmitz,S., Choudhury,B., Telford,W., Kapoor,V., Garfield,S., Howe,D., Gress,R.E. Exogenous insulin-like growth factor 1 enhances thymopoiesis predominantly through thymic epithelial cell expansion. Blood 2008; 112(-7-):2836-2846. >>> Insulin-like growth factor I; Sucrose; serum, mouse, PBS; SC; Mice; 4 weeks, 14 days; Pumps replaced after 2 weeks; peptides; animal info (C57BL/6, 8-12 wks old, thymectomized, PSGL-1KO).
P9063 Iikubo,M., Kobayashi,A., Kojima,I., Ikeda,H., Sakamoto,M., Sasano,T. Excessive lateral dental arch expansion in experimentally developed acromegaly-like rats. Archives of Oral Biology 2008; 53(-10-):924-927. >>> Insulin-like growth factor I, recomb. human; Saline; SC; Rat; 2002; 4 weeks; Controls received mp w/ vehicle; peptides; animal info (10 wks old, male, Wistar, 200-236 g.).
P8968 Zeinoaldin,S., Swarts,J.J.M., Van de Heijning,B.J.M. Central application of IGF-1 postpones time of vaginal opening in normally fed, but not in food-restricted rats. Hormone Research 2006; 66(-4-):169-174. >>> Insulin-like growth factor I, recomb. human; Acetic acid; BSA; CSF/CNS; Rat; 2002; 14 days; Controls received mp w/ saline; peptides; animal info (Wistar, female, 23 days old, 45 g.); cannula position confirmed with Evans blue dye post mortem; endocrinology.
P8932 Oya,S., Yoshikawa,G., Takai,K., Tanaka,J.I., Higashiyama,S., Saito,N., Kirino,T., Kawahara,N. Region-specific proliferative response of neural progenitors to exogenous stimulation by growth factors following ischemia. NeuroReport 2008; 19(-8-):805-810. >>> Epidermal growth factor, recomb. human; fibroblast growth factor-2, recomb. human; insulin-like growth factor I, recomb. human; erythropoietin, recomb. rat; brain-derived neurotrophic factor, recomb. human; DDL4, recomb. mouse; CSF/CNS; Rat; 1003D; 3 days; Ischemia; animal info (male, Wistar, 8wks old, 280-300 g.); bilateral infusion.
P8922 Escartin,C., Boyer,F., Bemelmans,A.P., Hantraye,P., Brouillet,E. IGF-1 exacerbates the neurotoxicity of the mitochondrial inhibitor 3NP in rats. Neuroscience Letters 2007; 425(-3-):167-172. >>> Insulin-like growth factor I; nitropropionic acid, 3-; Acetic acid; BSA; SC; Rat; 2001; 2ML1; 5 days; Controls received mp w/ vehicle; functionality of mp verified by plasma glucose; dose-response (fig. 1, pg. 169); ALZET brain infusion kit used; animal info (Lewis, 400 g.); neurodegenerative (Huntington’s Disease).
P8906 Todd,B.J., Fraley,G.S., Peck,A.C., Schwartz,G.J., Etgen,A.M. Central insulin-like growth factor 1 receptors play distinct roles in the control of reproduction, food intake, and body weight in female rats. Biology of Reproduction 2007; 77(-3-):492-503. >>> JB-1; insulin-like growth factor I, human; CSF, artificial; CSF/CNS; Rat; 1007D; 2002; 5, 7, 14 days; Controls received mp w/ vehicle; stress/adverse reaction: (see pg. 494) surgery led to a 10-15% loss of presurgical body weight, temporary disruption of estrous cycles; peptides; animal info (female, Sprague Dawley, 170-190 g.); IGF-1 receptor antagonist; cannula placement verified by dye injection at end of experiment; endocrinology.
P8871 Sferruzzi-Perri,A.N., Owens,J.A., Standen,P., Roberts,C.T. Maternal insulin-like growth factor-II promotes placental functional development via the type 2 IGF receptor in the guinea pig. PLACENTA 2008; 29(-4-):347-355. >>> Insulin-like growth factor II; Acetic acid; SC; Guinea-pig; 2002; 18 days; Controls received mp w/ vehicle; animal info (pregnant, female, 500g., 3-4 months old).
P8836 Nichols,T.C., Busby,WH Jr, Merricks,E., Sipos,J., Rowland,M., Sitko,K., Clemmons,D.R. Protease-resistant insulin-like growth factor (IGF)-Binding protein-4 inhibits IGF-I actions and neointimal expansion in a porcine model of neointimal hyperplasia. Endocrinology 2007; 148(-10-):5002-5010. >>> Insulin-like growth factor-binding protein-4; Insulin-like growth factor-binding protein-4, mutated; Insulin-like growth factor-1, recomb. human; PBS; IA (carotid); IA (femoral); Pig; 21 days; Controls received mp w/ vehicle; cardiovascular; peptides; animal info (male, female, spotted Poland/China, 12 months old); protease resistant mutant form of IGFBP-4.
P8827 Sinkevicius,K.W., Burdette,J.E., Woloszyn,K., Hewitt,S.C., Hamilton,K., Sugg,S.L., Temple,K.A., Wondisford,F.E., Korach,K.S., Woodruff,T.K., Greene,G.L. An estrogen receptor-alpha; knock-in mutation provides evidence of ligand-independent signaling and allows modulation of ligand-induced pathways in vivo. Endocrinology 2008; 149(-6-):2970-2979. >>> Insulin-like growth factor I, R3-; Acetic acid; IP; Mice; 1003D; 16-24 hours; Controls received IP vehicle or E2 injections; replacement therapy (ovariectomy); peptides; animal info (female, C57/BL6 wt, ENERKI, 12 wks old); endocrinology.
P8682 Sferruzzi-Perri,A.N., Owens,J.A., Standen,P., Taylor,R.L., Robinson,J.S., Roberts,C.T. Early pregnancy maternal endocrine insulin-like growth factor I programs the placenta for increased functional capacity throughout gestation. Endocrinology 2007; 148(-9-):4362-4370. >>> Insulin-like growth factor I; insulin-like growth factor II, recomb. human; Acetic acid; SC; Guinea-pig; 2002; 18 days; Controls received mp w/ vehicle; functionality of mp verified by plasma levels; animal info (pregnant, female, 500g, 3-4 weeks); endocrinology.
P8617 Carro,E., Trejo,J.L., Busiguina,S., Torres-Aleman,I. Circulating Insulin-Like Growth Factor I Mediates the Protective Effects of Physical Exercise against Brain Insults of Different Etiology and Anatomy. Journal of Neuroscience 2001; 21(-15-):5678-5684. >>> Antibody, anti-IGF-I; serum, rabbit; insulin-like growth factor I, recomb.; Saline; SC; Rat; mice; 1002; 2004; 4-6 weeks; 14 days; Controls received mp w/ normal rabbit serum; long-term study; peptides; animal info (male, C57BL/6, 25 grams, male, wistar, 250-300 grams).
P8614 Trejo,J.L., Carro,E., Torres-Aleman,I. Circulating Insulin-Like Growth Factor I Mediates Exercise-Induced Increases in the Number of New Neurons in the Adult Hippocampus. Journal of Neuroscience 2001; 21(-5-):1628-1634. >>> Insulin-like growth factor I; antiserum, anti-IGF-I; serum, normal rabbit; Saline; SC; Rat; 1002; 2001; 7,14 days; Controls received mp w/ vehicle or normal rabbit serum; peptides neurodegenerative (Alzheimer’s disease); animal info (male, Wistar, 300 grams).
P8592 Scheiwiller,E., Guler,H.P., Merryweather,J., Scandella,C., Maerki,W., Zapf,J., Froesch,E.R. Growth restoration of insulin-deficient diabetic rats by recombinant human insulin-like growth factor I. Nature 1986; 323(-6084-):169-171. >>> Insulin-like growth factor I, recomb. human; insulin; growth hormone, human; Saline; acetic acid; Rat; 2001; 6 days; Replacement therapy (STZ-induced diabetes); dose-response (fig. 1); peptides; animal info (male, Tif RAI, 120-130 grams); endocrinology.
P8387 Serose,A., Salmon,A., Fiszman,M.Y., Fromes,Y. Short-term treatment using insulin-like growth factor-1 (IGF-1) improves life expectancy of the delta-sarcoglycan deficient hamster. JOURNAL OF GENE MEDICINE 2006; 8(-8-):1048-1055. >>> Insulin-like growth factor I, recomb. human; SC; Hamster; 2002; 19 days; Controls received mp w/ Saline; cardiovascular; peptides; animal info (male, Syrian wt or CHF147, 7-8 months old, 100-150g.).
P8385 Sferruzzi-Perri,A.N., Owens,J.A., Standen,P., Taylor,R.L., Heinemann,G.K., Robinson,J.S., Roberts,C.T. Early treatment of the pregnant guinea pig with IGFs promotes placental transport and nutrient partitioning near term. AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM 2007; 292(-3-):E668-E676. >>> Insulin-like growth factor I; Insulin-like growth factor II, recomb. human; Acetic acid; SC; Guinea-Pig (pregnant); 2002; 18 days; Controls received mp w/ vehicle; functionality of mp verified by IGF-I/II maternal circulation levels; peptides; animal info (female, pregnant, 500g., 3-4 months old, gestation days 20-38).
P8370 Lopez-Lopez,C., Dietrich,M.O., Metzger,F., Loetscher,H., Torres-Aleman,I. Disturbed cross talk between insulin-like growth factor I and AMP-activated protein kinase as a possible cause of vascular dysfunction in the amyloid precursor protein/presenilin 2 mouse model of Alzheimer’s disease. Journal of Neuroscience 2007; 27(-4-):824-831. >>> Insulin-like growth factor I, recomb. human; SC; Mice; 1002; ; Controls received mp w/ saline; functionality of mp verified by serum IGF-I levels; peptides; animal info (C57BL/6J, APP/PS2, 6 month old); neurodegenerative (Alzheimer’s disease).
P8339 Schertzer,J.D., Lynch,G.S. Comparative evaluation of IGF-I gene transfer and IGF-I protein administration for enhancing skeletal muscle regeneration after injury. Gene Therapy 2006; 13(-23-):1657-1664. >>> Insulin-like growth factor I; SC; Mice; 1002; 3, 10, 14 days; Controls received non-coding plasmid; functionality of mp verified by residual volume; comparison of gene transfer vs. mp; peptides; animal info (male, C57BL10, 12-14 weeks old, myotoxic tibialis anterior muscle injury).
P8170 Kobayashi,A., Iikubo,M., Kojima,I., Ikeda,H., Sakamoto,M., Sasano,T. Morphological and histopathological changes in tongues of experimentally developed acromegaly-like rats. Hormone and Metabolic Research 2006; 38(-3-):146-151. >>> Insulin-like growth factor I, recomb. human; Saline; SC; Rat; 2002; 4 weeks; Controls received mp w/ vehicle; peptides; animal info (male, Wistar, 10 weeks old, 225 grams).
P8049 Kleinberg,D.L., Ruan,W.F., Yee,D., Kovacs,K.T., Vidal,S. Insulin-like growth factor (IGF)-I controls prostate fibromuscular development: IGF-I inhibition prevents both fibromuscular and glandular development in eugonadal mice. Endocrinology 2007; 148(-3-):1080-1088. >>> Insulin-like growth factor I; growth hormone, bovine; insulin-like growth factor-1, binding protein; SC; Mice; 1007D; 7 days; Controls received mp w/ saline; peptides; animal info (ORX, 10 weeks old, male); drugs delivered alone or in combination.

5. Nerve Growth Factor
Q2571 Mousa,S.A., Shaqura,M., Khalefa,B.I., Zoellner,C., Schaad,L., Schneider,J., Shippenberg,T.S., Richter,J.F., Hellweg,R., Shakibaei,M., Schaefer,M. Rab7 Silencing Prevents mu-Opioid Receptor Lysosomal Targeting and Rescues Opioid Responsiveness to Strengthen Diabetic Neuropathic Pain Therapy. Diabetes 2013; 62(-4-):1308-1319. >>> Nerve growth factor, beta; CSF, artificial; albumin, rat serum; CSF/CNS (intrathecal); Rat; 2001; 7 days; Control animals received mp w/ vehicle; animal info (Wistar, male, STZ induced diabetes).
Q2225 Aboulkassim,T., Tong,X.K., Tse,Y.C., Wong,T.P., Woo,S.B., Neet,K.E., Brahimi,F., Hamel,E., Saragovi,H.U. Ligand-Dependent TrkA Activity in Brain Differentially Affects Spatial Learning and Long-Term Memory. MOLECULAR PHARMACOLOGY 2011; 80(-3-):498-508. >>> Nerve growth factor, recomb; nerve growth factor TrkA agonist; CSF, artificial; CSF/CNS; Mice; 1002; 2 weeks; Controls received mp w/ vehicle; animal info (4-5 mo old, 670/671 KM-NL, 717 V-F); post op. care (buprenorphine); aCSF recipe; behavioral testing (Morris water maze test).
Q2205 Liu,J.H., Li,J.D., Lu,J., Xing,J.H., Li,J.H. Contribution of nerve growth factor to upregulation of P2X(3) expression in DRG neurons of rats with femoral artery occlusion. American Journal of Physiology-Heart and Circulatory Physiology 2011; 301(-3-):H1070-H1079. >>> Nerve growth factor; Saline; IM (hindlimb); Rat; 1003D; 3 days; Controls received mp w/ vehicle to opposite leg; animal info (Sprague Dawley, male, 5-7 wks old); “Note that the pumps were placed in the femoral triangle region and outlet of the pump was 2-3 mm distal to the inguinal ligament” pg H1071.
Q1986 Cabeza,C., Figueroa,A., Lazo,O.M., Galleguillos,C., Pissani,C., Klein,A., Gonzalez-Billault,C., Inestrosa,N.C., Alvarez,A.R., Zanlungo,S., Bronfman,F.C. Cholinergic Abnormalities, Endosomal Alterations and Up-Regulation of Nerve Growth Factor Signaling in Niemann-Pick Type C Disease. Molecular Neurodegeneration 2012; 7(-;-):U1-U18. >>> Nerve growth factor; CSF, artificial; CSF/CNS; Mice; 1002; 7 days; Controls received mp w/ vehicle; animal info (BALB/c, NPC/1 -/-); aCSF recipe; brain infusion kit used.
Q1126 Hu,Z.Q., Ulfendahl,M., Prieskorn,D.M., Olivius,P., Miller,J.M. Functional Evaluation of a Cell Replacement Therapy in the Inner Ear. OTOLOGY&NEUROTOLOGY 2009; 30(-4-):551-558. >>> Nerve growth factor; Hank’s based salt solution; albumin, guinea pig serum; Ear (cochlea); Guinea pig; 2002; ; Controls received mp w/ vehicle; animal info (pigmented, adult, 270-470 g); pumps replaced afer 13 days; post op. care (daily injections of cyclosporin and doxycycline); tissue perfusion.
Q0685 Toda,S., Sakai,A., Ikeda,Y., Sakamoto,A., Suzuki,H. A local anesthetic, ropivacaine, suppresses activated microglia via a nerve growth factor-dependent mechanism and astrocytes via a nerve growth factor-independent mechanism in neuropathic pain. Molecular Pain 2011; 7(-;-):U1-U11. >>> Nerve growth factor, beta, recomb., rat; Saline; albumin, rat, serum; CSF/CNS (intrathecal); Rat; 2001; 7 days; Controls received mp w/ vehicle; animal info (male, Sprague-Dawley, 220-300 g); chronic constrictive injury (CCI).
Q0682 Cirillo,G., Bianco,M.R., Colangelo,A.M., Cavaliere,C., Daniele,D., Zaccaro,L., Alberghina,L., Papa,M. Reactive astrocytosis-induced perturbation of synaptic homeostasis is restored by nerve growth factor. NEUROBIOLOGY OF DISEASE 2011; 41(-3-):630-639. >>> Nerve growth factor, beta, recomb.; GM6001; CSF, artificial; albumin, rat serum; CSF/CNS (intrathecal, subarachnoid space); Rat; 2001; 7 days; Controls received mp w/ vehicle; animal info (Sprague-Dawley, male, 250-300 g); enzyme inhibitor (metalloproteinase); PE10 connected to PE60 tubing.
Q0668 Beguin,P.C., El-Helou,V., Gillis,M.A., Duquette,N., Gosselin,H., Brugada,R., Villeneuve,L., Lauzier,D., Tanguay,J.F., Ribuot,C., Calderone,A. Nestin((+)) Stem Cells Independently Contribute to Neural Remodelling of the Ischemic Heart. Journal of Cellular Physiology 2011; 226(-5-):1157-1165. >>> Nerve growth factor, 2.5S; SC; Rat; 2ML1; 1 week; Controls received mp w/ saline; animal info (adult, male, Sprague-Dawley).
Q0544 Hobara,N., Yoshida,N., Goda,M., Yokomizo,A., Kitamura,Y., Sendou,T., Kawasaki,H. Neurotrophic Effect of Hepatic Growth Factor (HGF) on Reinnervation of Perivascular Calcitonin Gene-Related Peptide (CGRP)-Containing Nerves Following Phenol-Induced Nerve Injury in the Rat Mesenteric Artery. JOURNAL OF PHARMACOLOGICAL SCIENCES 2008; 108(-4-):495-504. >>> Hepatic growth factor, human; nerve growth factor; PBS; Triton-X; saline, sterile; IP; Rat; 2001; 7 days; Controls received mp w/ saline; animal info (8 wks old, Wistar).
Q0468 Conner,J.M., Franks,K.M., Titterness,A.K., Russell,K., Merrill,D.A., Christie,B.R., Sejnowski,T.J., Tuszynski,M.H. NGF Is Essential for Hippocampal Plasticity and Learning. Journal of Neuroscience 2009; 29(-35-):10883-10889. >>> Nerve growth factor, recomb. human; CSF, artificial; albumin, rat; CSF/CNS (septum); Rat; 2002; ; Controls received mp w/ vehicle; animal info (adult, female F344, 175-200 g, 3-4 months old); behavioral testing (Morris water maze test).
Q0157 Lazo,O.M., Mauna,J.C., Pissani,C.A., Inestrosa,N.C., Bronfman,F.C. Axotomy-induced neurotrophic withdrawal causes the loss of phenotypic differentiation and downregulation of NGF signalling, but not death of septal cholinergic neurons. Molecular Neurodegeneration 2010; 5(-;-):U1-U12. >>> Nerve growth factor; CSF, artificial; CSF/CNS; Rat; 2ML2; 14 days; Controls received mp w/ vehicle; animal info (Sprague Dawley, 280-300 g.); aCSF recipe; incorrectly stated 2002 pump.
Q0129 Goda,M., Atagi,S., Amitani,K., Hobara,N., Kitamura,Y., Kawasaki,H. Nerve Growth Factor Suppresses Prostate Tumor Growth. JOURNAL OF PHARMACOLOGICAL SCIENCES 2010; 112(-4-):463-466. >>> Nerve growth factor; SC; Mice (nude); 1002; 2 weeks; Controls received mp w/ saline; cancer (prostate); animal info (BALB/c, Slc, 5 wks old, nu/nu).
Q0009 Cirillo,G., Cavaliere,C., Bianco,M.R., De Simone,A., Colangelo,A.M., Sellitti,S., Alberghina,L., Papa,M. Intrathecal NGF Administration Reduces Reactive Astrocytosis and Changes Neurotrophin Receptors Expression Pattern in a Rat Model of Neuropathic Pain. Cellular and Molecular Neurobiology 2010; 30(-1-):51-62. >>> Nerve growth factor, b-, recomb. rat; CSF, artificial; CSF/CNS (intrathecal); Rat; 2001; 7 days; Controls received mp w/ vehicle; peptides; animal info (adult, male, Sprague-Dawley, 250-300 g); SCI; spinal cord injury; behavioral testing (thermal nociceptive testing, mechanical allodynia).
P9872 Unezaki,S., Yoshii,S., Mabuchi,T., Saito,A., Ito,S. Effects of neurotrophic factors on nerve regeneration monitored by in vivo imaging in thy1-YFP transgenic mice. Journal of Neuroscience Methods 2009; 178(-2-):308-315. >>> Nerve growth factor; glial-derived neurotrophic factor; Saline; CSF/CNS (sciatic nerve); Mice (transgenic); 1004; 4 weeks; Controls received mp w/ vehicle; half-life (p. 308) “short”; animal info (10 wks old, 20 g., Thy1-YEP); image of pump pg. 309; schematic of drug delivery system, fig. 1); “Because of the short biological half-life of neurotrophic factors, a delivery system that protects the protein and slowly releases it locally over a prolonged period of time is required.” pg. 308; tissue perfusion (sciatic nerve).
P9539 Xanthos,D.N., Kumar,N., Theodorsson,E., Coderre,T.J. The roles of nerve growth factor and cholecystokinin in the enhancement of morphine analgesia in a rodent model of central nervous system inflammation. Neuropharmacology 2009; 56(-3-):684-691. >>> Nerve growth factor, beta; CSF, artificial; CSF/CNS (intrathecal); Rat; 2001; 7 days; Controls received mp w/ vehicle; animal info (male, Long Evans, hooded).
P9516 Wissman,A.M., Brenowitz,E.A. The Role of Neurotrophins in the Seasonal-Like Growth of the Avian Song Control System. Journal of Neuroscience 2009; 29(-20-):6461-6471. >>> TrkB-Fc; TrkC-Fc; brain-derived neurotrophic factor; nerve growth factor; PBS; CSF/CNS (robust nucleus of the arcopallium); Bird; 1002; ; Controls received mp w/ vehicle; functionality of mp verified by residual volume; ALZET brain infusion kit 2 used; animal info (sparrow, adult, male, Gambel’s white crowned).
P9466 Xing,J.H., Lu,J., Li,J.H. Contribution of nerve growth factor to augmented TRPV1 responses of muscle sensory neurons by femoral artery occlusion. American Journal of Physiology-Heart and Circulatory Physiology 2009; 296(-5-):H1380-H1387. >>> Nerve growth factor; SC; Rat; 1003D; 72 hours; Controls received mp w/ saline to contralateral leg; cardiovascular; peptides; multiple pumps per animal (2); ischemia (muscle); animal info (male, Sprague Dawley, 5-7 wks old); SC in the hindlimb.
P9324 Averill,S., Inglis,J.J., King,V.R., Thompson,S.W.N., Cafferty,W.B.J., Shortland,P.J., Hunt,S.P., Kidd,B.L., Priestley,J.V. Reg-2 expression in dorsal root ganglion neurons after adjuvant-induced monoarthritis. Neuroscience 2008; 155(-4-):1227-1236. >>> Nerve growth factor, recomb. human; glial-derived neurotrophic factor, recomb. human; leukemia inhibitory factor, recomb. human; Saline; albumin, rat serum; CSF/CNS (intrathecal); Rat; 2002; 14 days; Controls received mp w/ vehicle; peptides, animal info (male, Wistar, 220-400 g.).
P9004 Clark,R.S.B., Nathaniel,P.D., Zhang,X.P., Dixon,C.E., Alber,S.M., Watkins,S.C., Melick,J.A., Kochanek,P.M., Graham,S.H. boc-Aspartyl(OMe)-fluoromethylketone attenuates mitochondrial release of cytochrome c and delays brain tissue loss after traumatic brain injury in rats. Journal of Cerebral Blood Flow and Metabolism 2007; 27(-2-):316-326. >>> Nerve growth factor; CSF, artificial; albumin, mouse; CSF/CNS (parietal cortex); Rat; 2002; 14 days; Controls received mp w/ vehicle; no stress (see pg. 321); peptides; cardiovascular; animal info (male, Sprague Dawley, 280-400 g., CCI brain injury); behavioral testing (beam balance, beam walking, Morris water maze).
P8890 Hobara,N., Goda,M., Yoshida,N., Takatori,S., Kitamura,Y., Mio,M., Kawasaki,H. Angiotensin II type 2 receptors facilitate reinnervation of phenol-lesioned vascular calcitonin gene-related peptide-containing nerves in rat mesenteric arteries. Neuroscience 2007; 150(-3-):730-741. >>> Angiotensin II; nerve growth factor; PD123319; losartan; Saline; water; IP; Rat; 2001; 7 days; Controls received mp w/ vehicle; functionality of mp verified by systolic blood pressure; peptides; post op. care (penicillin); animal info (8 wks old, Wistar).
P8576 Villoslada,P., Hauser,S.L., Bartke,I., Unger,J., Heald,N., Rosenberg,D., Cheung,S.W., Mobley,W.C., Fisher,S., Genain,C.P. Human Nerve Growth Factor Protects Common Marmosets against Autoimmune Encephalomyelitis by Switching the Balance of T Helper Cell Type 1 and 2 Cytokines within the Central Nervous System. Journal of Experimental Medicine 2000; 191(-10-):1799-1806. >>> Saline; nerve growth factor, recomb. human; cytochrome C; CSF/CNS; Marmoset; 2004; 35-42 days; Controls received mp w/ cytochrome C; functionality of mp verified by CSF levels of rhNGF; pumps replaced after 7-14 days of saline; immunology; ALZET brain infusion kit used; peptides; animal info (callithrix jacchus); “we chose to use an intracranial route to ensure accurate delivery of the drug into the CNS. This resulted in sustained elevated concentrations of rhNGF in the CSF of all rhNGF-treated animals.” (p. 1801).
P8526 Randolph,C.L., Bierl,M.A., Isaacson,L.G. Regulation of NGF and NT-3 protein expression in peripheral targets by sympathetic input. Brain Research 2007; 1144(–):59-69. >>> Nerve growth factor, mouse; Bisbenzimide; CSF/CNS; Rat; 2002; 2 weeks; Controls received no treatment; peptides; animal info (female, Sprague-Dawley, 3 months old); bisbenzimide (fluorescent marker) added to infusate to monitor cannula placement.
P8426 Hobara,N., Goda,M., Kitamura,Y., Sendou,T., Gomita,Y., Kawasaki,H. Adrenomedullin facilitates reinnervation of phenol-injured perivascular nerves in the rat mesenteric resistance artery. Neuroscience 2007; 144(-2-):721-730. >>> Adrenomedullin, recomb. human; nerve growth factor; Saline, sterile; IP; Rat; 2001; 7 days; Controls received mp w/ vehicle; dose-response (fig. 2); peptides; animal info (Wistar, 8 wk old, perivascular denervation).
P8023 Niewiadomska,G., Baksalerska-Pazera,M., Gasiorowska,A., Mietelska,A. Nerve growth factor differentially affects spatial and recognition memory in aged rats. Neurochemical Research 2006; 31(-12-):1481-1490. >>> Nerve growth factor, beta; CSF, artificial; CSF/CNS; Rat; 2004; 1 month; ALZET brain infusion kit used; post op. care (antibiotic and analgesic to scalp + fluid therapy); silastic tubing used; 28 G cannula.
P7978 Engelhardt,M., Di Cristo,G., Berardi,N., Maffei,L., Wahle,P. Differential effects of NT-4, NGF and BDNF on development of neurochemical architecture and cell size regulation in rat visual cortex during the critical period. European Journal of Neuroscience 2007; 25(-2-):529-540. >>> Nerve growth factor, mouse; NT-4, human recomb.; brain-derived neurotrophic factor, recomb. human; CSF/CNS (visual cortex); Rat; 1007D; 8 days; Post op. care (antibiotics and local anesthetics); animal info (Long-Evans); dental cement used; 30 G cannula used; tissue perfusion (visual cortex).
P7728 Frielingsdorf,H., Thal,L.J., Pizzo,D.P. The septohippocampal cholinergic system and spatial working memory in the Morris water maze. Behavioural Brain Research 2006; 168(-1-):37-46. >>> Nerve growth factor, recomb. human; CSF, artificial; gentamicin; albumin, rat serum; CSF/CNS; Rat; 2004; 4 weeks; Controls received mp w/ vehicle; functionality of mp verified by residual volume; cannula placement confirmed by cresyl violet staining; peptides; animal info (male, Fisher 344, 13-14 wk. old, medial septum lesion, 400g); mp primed 2 days in 37 Celsius saline.
P7582 Cardoso,A., Paula-Barbosa,M.M., Lukoyanov,N.V. Reduced density of neuropeptide Y neurons in the somatosensory cortex of old male and female rats: Relation to cholinergic depletion and recovery after nerve growth factor treatment. Neuroscience 2006; 137(-3-):937-948. >>> Dye, methylene blue; nerve growth factor; CSF, artificial; BSA; CSF/CNS; Rat; 2002; 14 days; Controls received mp w/ vehicle or sham surgery; functionality of mp verified by pretesting; Alzet brain infusion kit used; post op. care (antiseptic); animal info (male, female, Wistar 6 month old, 24 month old); Lynch coil filled with NGF, air-oil spacer between mp and catheter, mp filled with dye.

6. Placental Growth Factor
Q0490 Takeda,Y., Uemura,S., Iwama,H., Imagawa,K.I., Nishida,T., Onoue,K., Takemoto,Y., Soeda,T., Okayama,S., Somekawa,S., Ishigami,K.I., Takaoka,M., Kawata,H., Kubo,A., Horii,M., Nakajima,T., Saito,Y. Treatment With Recombinant Placental Growth Factor (PIGF) Enhances Both Angiogenesis and Arteriogenesis and Improves Survival After Myocardial Infarction. CIRCULATION JOURNAL 2009; 73(-9-):1674-1682. >>> Placental growth factor, recomb. human; flt-1, recomb. human, soluble; IP; Mice; 3, 7 days; Controls received mp w/ vehicle; animal info (C57BL/6, 12 wks old); polyethylene IP catheter used.
P6669 Tamarat,R., Silvestre,J.S., Ricousse-Roussanne,S., Barateau,V., Lecomte-Raclet,L., Clergue,M., Duriez,M., Tobelem,G., Levy,B.I. Impairment in ischemia-induced neovascularization in diabetes – Bone marrow mononuclear cell dysfunction and therapeutic potential of placenta growth factor treatment. American Journal of Pathology 2004; 164(-2-):457-466. >>> Placental growth factor; SC; Mice; 2001; 14 days; Diabetes, placenta growth factor (PIGF) is a VEGF homologue; ischemia.

7. Transforming Growth Factor
Q2327 Chim,H., Miller,E., Gliniak,C., Alsberg,E. Stromal-cell-derived factor (SDF) 1-alpha in combination with BMP-2 and TGF-beta1 induces site-directed cell homing and osteogenic and chondrogenic differentiation for tissue engineering without the requirement for cell seeding. Cell and Tissue Research 2012; 350(-1-):89-94. >>> Stromal-cell-derived factor-1, alpha; bone morphogenetic protein 2; transforming growth factor-1, beta; IP (abdominal wall); Rat; 2004; 4 weeks; Negative control animals received no cytokines; animal info (Sprague Dawley, adult); “A custom-made apparatus for the constant delivery of cytokines was assembled consisting in a microneedle system and Alzet osmotic pump” pg 90; fig 1b, image of custom-made cytokine delivery apparatus; tissue perfusion (anterior abdominal wall).
Q2324 Holmberg,C., Quante,M., Steele,I., Kumar,J.D., Balabanova,S., Duval,C., Czepan,M., Rakonczay,Z.Jr, Tiszlavicz,L., Nemeth,I., Lazar,G., Simonka,Z., Jenkins,R., Hegyi,P., Wang,T.C., Dockray,G.J., Varro,A. Release of TGF beta ig-h3 by gastric myofibroblasts slows tumor growth and is decreased with cancer progression. Carcinogenesis 2012; 33(-8-):1553-1562. >>> Transforming growth factor-beta-induced gene h3; Mice; ; Animal info (SCID, 6-8 wks old); cancer.
Q1643 Kandasamy,M., Couillard-Despres,S., Raber,K.A., Stephan,M., Lehner,B., Winner,B., Kohl,Z., Rivera,F.J., Nguyen,H.P., Riess,O., Bogdahn,U., Winkler,J., von Hoersten,S., Aigner,L. Stem Cell Quiescence in the Hippocampal Neurogenic Niche Is Associated With Elevated Transforming Growth Factor-beta Signaling in an Animal Model of Huntington Disease. Journal of Neuropathology and Experimental Neurology 2010; 69(-7-):717-728. >>> Transforming growth factor, beta 1, recomb.; CSF, artificial; CSF/CNS; Rat; 2002; 14 days; Controls received mp w/ vehicle; animal info (Fischer 344, female, 2-3 mo old, 180 g).
Q1047 Echeverry,S., Shi,X.Q., Rivest,S., Zhang,J. Peripheral Nerve Injury Alters Blood-Spinal Cord Barrier Functional and Molecular Integrity through a Selective Inflammatory Pathway. Journal of Neuroscience 2011; 31(-30-):10819-10828. >>> Minocycline hydrochloride; MCP-1, recomb., rat; antibody, MCP-1 neutralizing; IL-10, recomb.; transforming growth factor, beta-1; Saline, sterile, isotonic; CSF/CNS (intrathecal); Rat; 2001; 3, 7 days; Controls received mp w/ vehicle; animal info (male, Sprague Dawley, 250-275 g, naive, nerve-injured).
Q0790 Leker,R.R., Toth,Z.E., Shahar,T., Cassiani-Ingoni,R., Szalayova,I., Key,S., Bratincsak,A., Mezey,E. TRANSFORMING GROWTH FACTOR alpha INDUCES ANGIOGENESIS AND NEUROGENESIS FOLLOWING STROKE. Neuroscience 2009; 163(-1-):233-243. >>> Transforming growth factor, alpha; CSF, artificial; CSF/CNS (infarct border); Mice; 1002; 14 days; Controls received mp w/ vehicle; animal info (C57B, male, 4-6 wks old).
P9873 Echeverry,S., Shi,X.Q., Haw,A., Liu,H., Zhang,Z., Zhang,J. Transforming growth factor-beta-1 impairs neuropathic pain through pleiotropic effects. Molecular Pain 2009; 5(-;-):U1-U18. >>> Transforming growth factor-1, beta; CSF/CNS (intrathecal); Rat; 1007D; 2002; 7, 14 days; Animal info (male, Sprague Dawley, 250-275 g); incorrectly stated pump model as 2002D.
P9848 McGrath,L.J., Ingman,W.V., Robker,R.L., Robertson,S.A. Exogenous transforming growth factor beta1 replacement and fertility in male Tgfb1 null mutant mice. REPRODUCTION FERTILITY AND DEVELOPMENT 2009; 21(-4-):561-570. >>> Transforming growth factor beta-1, recomb. human; BSA; PBS; SC; Mice; 1002; 2 weeks; Controls received mp w/ vehicle; comparios of PO gavage vs. mp; half-life (p. 563) 1 hour; animal info (Tgfb1 null); “continuous supply of rhLTGFB1 by subcutaneous insertion of osmotic pumps successfully increased circulating TGFB1 to detectable levels” pg. 568.
P9807 Guerra-Crespo,M., Gleason,D., Sistos,A., Toosky,T., Solaroglu,I., Zhang,J.H., Bryant,P.J., Fallon,J.H. TRANSFORMING GROWTH FACTOR-ALPHA INDUCES NEUROGENESIS AND BEHAVIORAL IMPROVEMENT IN A CHRONIC STROKE MODEL. Neuroscience 2009; 160(-2-):470-483. >>> Transforming growth factor; CSF/CNS; Rat; 2004; 28 days; Controls received mp w/ PBS; ALZET brain infusion kit used; animal info (90 days old, MCAO); behavioral testing (cylinder corner test).
P9772 Cooper,O., Isacson,O. Intrastriatal Transforming Growth Factor Delivery to a Model of Parkinson’s Disease Induces Proliferation and Migration of Endogenous Adult Neural Progenitor Cells without Differentiation into Dopaminergic Neurons. The Journal of Neuroscience 2004; 24(-41-):8924-8931. >>> Transforming growth factor, alpha; PBS; CSF/CNS (striatum); Rat; 2004; 1, 2, 4 weeks; Controls received mp w/ vehicle; ALZET brain infusion kit 2 used; animal info (naive, adult, male, Sprague Dawley); neurodegenerative (Parkinson’s Disease); brain tissue distribution; tissue perfusion (striatum).
P9532 Dufour,C., Holy,X., Marie,P.J. Transforming growth factor-beta prevents osteoblast apoptosis induced by skeletal unloading via PI3K/Akt, Bcl-2, and phospho-Bad signaling. J Physiol Endocrinol Metab 2008; (-294-):E794-E801. >>> Transforming growth factor-beta 2; Rat; 2, 4, 7 days; Animal info (adult, 4 wks old, Wistar, 130g.).
P9402 de Chevigny,A., Cooper,O., Vinuela,A., Reske-Nielsen,C., Lagace,D.C., Eisch,A.J., Isacson,O. Fate mapping and lineage analyses demonstrate the production of a large number of striatal neuroblasts after transforming growth factor alpha and noggin striatal infusions into the dopamine-depleted striatum. Stem Cells 2008; 26(-9-):2349-2360. >>> Transforming growth factor-a; noggin; PBS; CSF/CNS (striatum); Rat; 1002; 2004; 14, 28, 41 days; Controls received mp w/ vehicle; ALZET brain infusion kit 2 used; brain tissue distribution; peptides; animal info (female, Sprague Dawley, 250-300 g.); behavioral testing (rotation behavior); noggin is a bone morphogenetic protein antagonist; neurodegenerative (Parkinson’s Disease).
P9315 Gleason,D., Fallon,J.H., Guerra,M., Liu,J.C., Bryant,P.J. Ependymal stem cells divide asymmetrically and transfer progeny into the subventricular zone when activated by injury. Neuroscience 2008; 156(-1-):81-88. >>> Transforming growth factor-a; PBS; CSF/CNS (caudate putamen); Rat; 1, 3, 5, 7, 28 days; Peptides, animal info (male, 10 wks old); neurodegenerative (Parkinson’s Disease); neural stem cell research.
P9186 White,R.E., Yin,F.Q., Jakeman,L.B. TGF-alpha increases astrocyte invasion and promotes axonal growth into the lesion following spinal cord injury in mice. Experimental Neurology 2008; 214(-1-):10-24. >>> Transforming growth factor-alpha; Serum, mouse; PBS; CSF/CNS (intrathecal); Mice; 2002; 14 days; Controls received mp w/ vehicle; functionality of mp verified by residual volume; post op. care (Baytril); animal info (female, adult, C57BL/6, 10 wks old, 17-20 g.); spinal cord injury; pumps were primed in saline at 37 degree Celsius for 24 hours; pumps were weighed before and after filling; good methods; PE-50 used for catheter.
P8988 Wachs,F.P., Winner,B., Couillard-Despres,S., Schiller,T., Aigner,R., Winkler,J., Bogdahn,U., Aigner,L. Transforming growth factor-beta 1 is a negative modulator of adult neurogenesis. Journal of Neuropathology and Experimental Neurology 2006; 65(-4-):358-370. >>> Transforming growth factor-B1, recomb.; CSF, artificial; CSF/CNS; Rat; 2002; 7 days; Controls received mp w/ vehicle; peptides; animal info (female, Fischer-344, 2-3 months old, 180 g.).

8. Vascular Endothelial Growth Factor
Q2611 Siddiqui,A.H., Irani,R.A., Zhang,W.R., Wang,W., Blackwell,S.C., Kellems,R.E., Xia,Y. Angiotensin Receptor Agonistic Autoantibody-Mediated Soluble Fms-Like Tyrosine Kinase-1 Induction Contributes to Impaired Adrenal Vasculature and Decreased Aldosterone Production in Preeclampsia. Hypertension 2013; 61(-2-):472-U526. >>> Vascular endothelial growth factor, 121; Mice (pregnant); 5 days; Animal info (C57BL/6).
Q2593 Shan,L., Yong,H.M., Song,Q., Wei,Y., Qin,R., Zhang,G.H., Xu,M.Y., Zhang,S.H. Vascular endothelial growth factor B prevents the shift in the ocular dominance distribution of visual cortical neurons in monocularly deprived rats. Experimental Eye Research 2013; 109(-;-):17-21. >>> Vascular endothelial growth factor B; CSF, artificial; CSF/CNS; Rat; 1007D; ; Control animals received mp w/ vehicle; animal info (Long Evans hooded); PE60 tubing used.
Q2468 Xiao,X.W., Guo,P., Chen,Z., El-Gohary,Y., Wiersch,J., Gaffar,I., Prasadan,K., Shiota,C., Gittes,G.K. Hypoglycemia Reduces Vascular Endothelial Growth Factor A Production by Pancreatic Beta Cells as a Regulator of Beta Cell Mass. Journal of Biological Chemistry 2013; 288(-12-):8636-8646. >>> Vascular endothelial growth factor, A; Mice; 2004; ; Animal info (C57BL/6, MIP-GFP, male, 8 wks old);.
Q2316 Argandona,E.G., Bengoetxea,H., Bulnes,S., Rico-Barrio,I., Ortuzar,N., Lafuente,J.V. Effect of intracortical vascular endothelial growth factor infusion and blockade during the critical period in the rat visual cortex. Brain Research 2012; 1473(-;-):141-154. >>> Vascular endothelial growth factor; anti-VEGF; PBS; CSF/CNS (cortex); Rat; 1007D; ; Control animals received mp w/ vehicle; animal info (Long Evans, P18); ALZET brain infusion kit used; cyanoacrylate adhesive used.
Q2201 Mateus,J., Bytautiene,E., Lu,F.X., Tamayo,E.H., Betancourt,A., Hankins,G.D.V., Longo,M., Saade,G.R. Endothelial growth factor therapy improves preeclampsia-like manifestations in a murine model induced by overexpression of sVEGFR-1. American Journal of Physiology-Heart and Circulatory Physiology 2011; 301(-5-):H1781-H1787. >>> Vascular endothelial growth factor 121; PBS; SC; Mice (pregnant); 2002; 10 days; Controls received mp w/ vehicle; animal info (CD-1); functionality of mp verified by residual volume and plasma drug levels.
Q1819 Thau-Zuchman,O., Shohami,E., Alexandrovich,A.G., Leker,R.R. SUBACUTE TREATMENT WITH VASCULAR ENDOTHELIAL GROWTH FACTOR AFTER TRAUMATIC BRAIN INJURY INCREASES ANGIOGENESIS AND GLIOGENESIS. Neuroscience 2012; 202(-;-):334-341. >>> Vascular endothelial growth factor; Saline; CSF/CNS; Mice; 7 days; Controls received mp w/ vehicle; animal info (adult, Sabra, 40 g).
Q1810 Herz,J., Reitmeir,R., Hagen,S.I., Reinboth,B.S., Guo,Z.Y., Zechariah,A., ElAli,A., Doeppner,T.R., Bacigaluppi,M., Pluchino,S., Kilic,U., Kilic,E., Hermann,D.M. Intracerebroventricularly delivered VEGF promotes contralesional corticorubral plasticity after focal cerebral ischemia via mechanisms involving anti-inflammatory actions. NEUROBIOLOGY OF DISEASE 2012; 45(-3-):1077-1085. >>> Vascular endothelial growth factor, recomb. human; CSF/CNS; Mice; 2002; 2004; 4 weeks; Controls received mp w/ saline; animal info (male, C57BL/6J, 8-10 wks old, 23-25 g); ischemia.
Q1775 Lutton,C., Young,Y.W., Williams,R., Meedeniya,A.C.B., kay-Sim,A., Goss,B. Combined VEGF and PDGF Treatment Reduces Secondary Degeneration after Spinal Cord Injury. Journal of Neurotrauma 2012; 29(-5-):957-U479. >>> Vascular endothelial growth factor; platelet-derived growth factor; Saline; CSF/CNS (intrathecal); Rat; 2001; 7 days; Controls received mp w/ vehicle; animal info (Wistar, male, adult, 300 g, 20-25 wks old); pump functionality verified in vitro; “catheter was… sutured to the muscle to keep it in place” pg 959.
Q1664 Chu,L.M., Robich,M.P., Lassaletta,A.D., Feng,J., Laham,R.J., Burgess,T., Clements,R.T., Sellke,F.W. Resveratrol supplementation abrogates pro-arteriogenic effects of intramyocardial vascular endothelial growth factor in a hypercholesterolemic swine model of chronic ischemia. Surgery 2011; 150(-3-):390-399. >>> Vascular endothelial growth factor, recomb. human; Intrapericardial; Pig; ; Animal info (intact, male, Yorkshire); stress/adverse effects “sudden cardiac death”, pg 393.
Q1655 Thau-Zuchman,O., Shohami,E., Alexandrovich,A.G., Leker,R.R. Combination of Vascular Endothelial and Fibroblast Growth Factor 2 for Induction of Neurogenesis and Angiogenesis after Traumatic Brain Injury. Journal of Molecular Neuroscience 2012; 47(-1-):166-172. >>> Vascular endothelial growth factor; Saline; CSF/CNS; Mice; 1007D; 7 days; Controls received mp w/ vehicle; animal info (male, Sabra, adult, 40 g).
Q1620 Reitmeir,R., Kilic,E., Reinboth,B.S., Guo,Z.Y., ElAli,A., Zechariah,A., Kilic,U., Hermann,D.M. Vascular endothelial growth factor induces contralesional corticobulbar plasticity and functional neurological recovery in the ischemic brain. Acta Neuropathologica 2012; 123(-2-):273-284. >>> Vascular endothelial growth factor; NaCl; CSF/CNS; Mice; 2002; 2004; 4 weeks; Controls received mp w/ vehicle; animal info (male, C57Bl6/j, 8-10 wks old, 23-25 g); ischemia (MCAO); stress/adverse effects, “complications related to pump insertion” pg 274; behavioral testing (Rotarod, grip strength test).
Q1592 Romo,L.B., Tapia,R. VEGF protects spinal motor neurons against chronic excitotoxic degeneration in vivo by activation of PI3-K pathway and inhibition of p38MAPK. Journal of Neurochemistry 2010; 115(-5-):1090-1101. >>> Isoxazolepropionate, alpha amino-3-hydroxy-5-; vascular endothelial growth factor, recomb., 164; SU14980, tyrphostin; LY294002; wortmannin; PD98059; SB203580; PBS; DMSO; CSF/CNS (intrathecal, spinal cord); Rat; 2004; 2, 10, 20 days; Controls received mp w/ vehicle; animal info (Wistar, male, 270-290 g, adult); alpha amino-3-hydroxy-5-isoxazolepropionate also known as AMPA; wound clips used; post op. care, pg 1091 (penicillin); good methods, pg 1091; multiple pumps used (2); multiple intrathecal catheters used; wound clips used; 2% DMSO used; enzyme inhibitor (p38 mitogen-activated protein kinase, p38MAPK).
Q1355 Thau-Zuchman,O., Shohami,E., Alexandrovich,A.G., Leker,R.R. Vascular endothelial growth factor increases neurogenesis after traumatic brain injury. Journal of Cerebral Blood Flow and Metabolism 2010; 30(-5-):1008-1016. >>> Vascular endothelial growth factor; CSF/CNS; Mice; 6, 7 days; Controls received mp w/ vehicle or were sham operated; animal info (adult, Sabra, male, 40 g); infusion rate of 0.5 ul/hr.
Q1347 Siddiqui,A.H., Irani,R.A., Zhang,Y.J., Dai,Y.B., Blackwell,S.C., Ramin,S.M., Kellems,R.E., Xia,Y. Recombinant Vascular Endothelial Growth Factor 121 Attenuates Autoantibody-Induced Features of Pre-eclampsia in Pregnant Mice. American Journal of Hypertension 2011; 24(-5-):606-612. >>> Vascular endothelial growth factor 121; SC; Mice (pregnant); 1007D; 5 days; Animal info (C57BL/6, 8 wks old).
Q1236 Miyasaka,E.A., Raghavan,S., Gilmont,R.R., Mittal,K., Somara,S., Bitar,K.N., Teitelbaum,D.H. In vivo growth of a bioengineered internal anal sphincter: comparison of growth factors for optimization of growth and survival. PEDIATRIC SURGERY INTERNATIONAL 2011; 27(-2-):137-143. >>> Fibroblast growth factor-2; vascular endothelial growth factor-2; platelet-derived growth factor; SC; Mice; 1004; 28 days; Controls received mp with no growth factors; animal info (C57BL/6); good methods, pg 138; tissue perfusion (internal anal sphincter); silicone catheter used; “the osmotic pumps we used completed delivery of the growth factors by 28 days, which would clearly limit the duration of exposure to the growth factor, lessening the risk of malignancy” pg 143.
Q1197 Lee,C., Agoston,D.V. Vascular Endothelial Growth Factor Is Involved in Mediating Increased De Novo Hippocampal Neurogenesis in Response to Traumatic Brain Injury. Journal of Neurotrauma 2010; 27(-3-):541-553. >>> Vascular endothelial growth factor 164; SU5416; uridine, bromodeoxy; CSF, artificial; DMSO; CSF/CNS; Rat; 2002; 13 days; Controls received mp w/ vehicle; animal info (young, Sprague Dawley, male, 270-300 g); 1% DMSO used.
Q0878 Ortuzar,N., Argandona,E.G., Bengoetxea,H., Lafuente,J.V. Combination of intracortically administered VEGF and environmental enrichment enhances brain protection in developing rats. Journal of Neural Transmission 2011; 118(-1-):135-144. >>> Vascular endothelial growth factor; CSF/CNS (cortex); Rat; 1007D; 7 days; Controls received mp w/ PBS or no implantation; animal info (Long-Evans, P18); cyanoacrylate adhesive; ALZET brain infusion kit 3 used; “Total operating time was approximately 25 min.” pg 137.
Q0712 Nicoletti,J.N., Lenzer,J., Salerni,E.A., Shah,S.K., Elkady,A., Khalid,S., Quinteros,D., Rotella,F., Betancourth,D., Croll,S.D. Vascular endothelial growth factor attenuates status epilepticus-induced behavioral impairments in rats. EPILEPSY&BEHAVIOR 2010; 19(-3-):272-277. >>> Vascular endothelial growth factor, 165, recomb. human; vascular endothelial growth factor, inactivated; PBS, sterile; CSF/CNS (hippocampus); Rat; 2002; 2 weeks; Controls received no surgical manipulations or protein infusions; animal info (male Sprague-Dawley, 250-350 g); behavioral testing (Morris water maze, Grid locomotor activity, Light-dark exploration).
Q0514 Lee,C., Agoston,D.V. Inhibition of VEGF receptor 2 increased cell death of dentate hilar neurons after traumatic brain injury. Experimental Neurology 2009; 220(-2-):400-403. >>> Vascular endothelial growth factor (164); SU5416; CSF, artificial; DMSO; CSF/CNS; Rat; 1002; 13 days; Controls received mp w/ vehicle; animal info (young, male, Sprague Dawley, 270-330 g.); cannula placement verified by histology; 1% DMSO used; artificial CSF recipe.
Q0400 Bogaert,E., Van Damme,P., Poesen,K., Dhondt,J., Hersmus,N., Kiraly,D., Scheveneels,W., Robberecht,W., Van den Bosch,L. VEGF protects motor neurons against excitotoxicity by upregulation of GluR2. NEUROBIOLOGY OF AGING 2010; 31(-12-):2185-2191. >>> Vascular endothelial growth factor; CSF/CNS; Rat; 2004; 1 week; Controls received mp w/ vehicle; animal info (80 days old).
Q0354 Ahmed,A., Singh,J., Khan,Y., Seshan,S.V., Girardi,G. A New Mouse Model to Explore Therapies for Preeclampsia. PLoS One 2010; 5(-10-):U325-U333. >>> Vascular endothelial growth factor (121); PBS, sterile; SC; Mice; 7 days; Animal info (CBA/J x DBA/2 and CBA/J x BALB/c).
Q0282 Schmidt,C., Bezuidenhout,D., Beck,M., Van der Merwe,E., Zilla,P., Davies,N. Rapid three-dimensional quantification of VEGF-induced scaffold neovascularisation by microcomputed tomography. Biomaterials 2009; 30(-30-):5959-5968. >>> Vascular endothelial growth factor (165); SC; Rat; 1002; 10 days; Controls received mp w/ PBS; animal info (male, Wistar, 234-254 g); functionality of mp verified by residual volume; post op. care (buprenorphine); pump connected to a porous polyurethane construct, schematic on Figure 1A;.
P9814 Santulli,G., Ciccarelli,M., Palumbo,G., Campanile,A., Galasso,G., Ziaco,B., Altobelli,G.G., Cimini,V., Piscione,F., D’Andrea,L.D., Pedone,C., Trimarco,B., Iaccarino,G. In vivo properties of the proangiogenic peptide QK. Journal of Translational Medicine 2009; 7(-;-):U1-U10. >>> Vascular endothelial growth factor-15; vascular endothelial growth factor-165; QK; IA (femoral); Rat; 2002; 14 days; Peptides; animal info (12 wks old, WKY, normosensitive); QK is a de novo engineered VEGF mimicking peptide.
P9708 Schmidt,N.O., Koeder,D., Messing,M., Mueller,F.J., Aboody,K.S., Kim,S.U., Black,P.M., Carroll,R.S., Westphal,M., Lamszus,K. Vascular endothelial growth factor-stimulated cerebral microvascular endothelial cells mediate the recruitment of neural stem cells to the neurovascular niche. Brain Research 2009; 1268(-;-):24-37. >>> Vascular endothelial growth factor, recomb. human; CSF/CNS (parenchyma); Mice (nude); 2004; ; Controls received mp w/PBS; animal info (6 wks old).
P9443 Segi-Nishida,E., Warner-Schmidt,J.L., Duman,R.S. Electroconvulsive seizure and VEGF increase the proliferation of neural stem-like cells in rat hippocampus. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2008; 105(-32-):11352-11357. >>> Vascular endothelial growth factor 164, recomb. rat; PBS; CSF/CNS; Rat; 1003D; 3 days; 24 hours; Controls received mp w/ vehicle; brain tissue distribution; peptides; animal info (male, Sprague Dawley, 175-200 g.); delayed delivery (in the 48 hour infusion, PBS infused for 24 hours to “avoid the influence of cannulation and anesthesia.” (p. 11354) then VEGF infused for 24 hours).
P9248 Poesen,K., Lambrechts,D., Van Damme,P., Dhondt,J., Bender,F., Frank,N., Bogaert,E., Claes,B., Heylen,L., Verheyen,A., Raes,K., Tjwa,M., Eriksson,U., Shibuya,M., Nuydens,R., Van den Bosch,L., Meert,T., D’Hooge,R., Sendtner,M., Robberecht,W., Carmeliet,P. Novel Role for Vascular Endothelial Growth Factor (VEGF) Receptor-1 and Its Ligand VEGF-B in Motor Neuron Degeneration. Journal of Neuroscience 2008; 28(-42-):10451-10459. >>> Vascular endothelial growth factor-B186, recomb. mouse; CSF, artificial; CSF/CNS; Rat; 2004; 100 days; Controls received mp w/ vehicle; long-term study; pumps replaced every 25 days; no stress (see pg. 10456); stability verified by 4 weeks in mp at 37 degrees Celsius; animal info (HAN-Wistar x Sprague Dawley-hSOD1G93A, 60 days old); behavioral testing (Rotarod test); “this delivery route was chosen because previous studies demonstrated that intracerebroventricularly delivered VEGF diffuses from the CSF into the neural parenchyma, where it reaches it’s target motor neurons.” (p. 10456).
P9198 Rennel,E.S., Hamdollah-Zadeh,M.A., Wheatley,E.R., Magnussen,A., Schueler,Y., Kelly,S.P., Finucane,C., Ellison,D., Cebe-Suarez,S., Ballmer-Hofer,K., Mather,S., Stewart,L., Bates,D.O., Harper,S.J. Recombinant human VEGF165b protein is an effective anti-cancer agent in mice. European Journal of Cancer 2008; 44(-13-):1883-1894. >>> Vascular endothelial growth factor-165-b, recomb.; NaCl, sterile; SC; Mice; 28 days; No stress (see pg. 1888); half-life (p. 1893) 25 min in mice, 13.8-72 min in rats; cancer (colon); post op. care (Temgesic); animal info (C57/Bl6, 720 g.); silk sutures used; “no adverse effects were observed with this infusion of VEGF165b” pg. 1888; compound is an anti angiogenic isoform of VEGF.
P9139 Nicoletti,J.N., Shah,S.K., McCloskey,D.P., Goodman,J.H., Elkady,A., Atassi,H., Hylton,D., Rudge,J.S., Scharfman,H.E., Croll,S.D. Vascular endothelial growth factor is up-regulated after status epilepticus and protects against seizure-induced neuronal loss in hippocampus. Neuroscience 2008; 151(-1-):232-241. >>> Vascular endothelial growth factor, recomb. human; BowAng1; Flt-Fc; CSF/CNS (dorsal hippocampus); Rat; 5 days; Controls received mp w/ PBS; animal info (male, Sprague Dawley, adult, 250-350 g.); cannula, polyvinyl catheter from Plastics One used; BowAng1 is a fusion of four molecules of angiopoietin-1 with two molecules of hFC; Flt-Fc is an immunoadhesin.
P9097 Ohm,J.E., Gabrilovich,D.I., Sempowski,G.D., Kisseleva,E., Parman,K.S., Nadaf,S., Carbone,D.P. VEGF inhibits T-cell development and may contribute to tumor-induced immune suppression. Blood 2003/6/15; 101(-12-):4878-4886. >>> Vascular endothelial growth factor; SC; Mice (transgenic); 7-28 days; Controls received mp w/ PBS; no stress (see pg. 4880); animal info (female, 6-8 wks old, DO11.10); immunology.
P8833 Boodhwani,M., Voisine,P., Rue,M., Sodha,N.R., Feng,J., Xu,S.H., Bianchi,C., Settke,F.W. Comparison of vascular endothelial growth factor and fibroblast growth factor-2 in a swine model of endothelial dysfunction. European Journal of Cardio-thoracic Surgery 2008; 33(-4-):645-650. >>> Vascular endothelial growth factor 165, recomb. human; Heparin; Intramyocardial; Pig (miniswine); 2ML4; 4 weeks; Tissue perfusion (myocardial); half-life (p. 649) “short”; cardiovascular; peptides; ischemia (cardiac); animal info (Yucatan mini-swine, 20-30 kg.).
P8799 Tsuchiya,A., Heike,T., Baba,S., Fujino,H., Umeda,K., Matsuda,Y., Nomoto,M., Ichida,T., Aoyagi,Y., Nakahata,T. Sca-1+ endothelial cells (SPECs) reside in the portal area of the liver and contribute to rapid recovery from acute liver disease. Biochemical and Biophysical Research Communications 2008; 365(-3-):595-601. >>> Vascular endothelial growth factor-inhibitor; DMSO; IP; Mice; 9, 11 days; Controls received mp w/ vehicle; animal info (C57BL/6; 4, 8, 12 wks old; anti-Fas Ab-induced liver damage); agent also known as CBO-P11.
P8512 Huang,Y., Chen,X., Dikov,M.M., Novitskiy,S.V., Mosse,C.A., Yang,L., Carbone,D.P. Distinct roles of VEGFR-1 and VEGFR-2 in the aberrant hematopoiesis associated with elevated levels of VEGF. Blood 2007; 110(-2-):624-. >>> Vascular endothelial growth factor 165, recomb. human; vascular endothelial growth factor, receptor-2 selective; vascular endothelial growth factor, receptor-1 selective; Mice; 2004; 28 days; Controls received mp w/ PBS; cancer; peptides; animal info (female, Balb/c, 6-8 weeks old); angiogenesis; hematology.
P8366 Dorrell,M.I., Aguilar,E., Scheppke,L., Barnett,F.H., Friedlander,M. Combination angiostatic therapy completely inhibits ocular and tumor angiogenesis. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2007; 104(-3-):967-972. >>> Vascular endothelial growth factor, aptamer; EMD472523; T2-TrpRS; PBS; CSF/CNS (intratumoral); Rat; 2001D; 2ML2; 2ML4; 3,6 days; 24 hours; Controls received mp w/ vehicle; cancer (gliosarcoma); animal info (male, Fischer, 344); EMD472523 is an integrin antagonist, VEGF aptamer is chemically identical to Macugen; T2 is a proteolytic fragment of tryptophan tRNA synthetase; all agents have angiostatic activity; tissue perfusion (tumor).
P8306 Tiranathanagul,K., Dhawan,V., Lytle,I.F., Zhang,W., Borschel,G.H., Buffington,D.A., Tziampazis,E., Brown,D.L., Humes,H.D. Tissue engineering of an implantable bioartificial hemofilter. ASAIO Journal 2007; 53(-2-):176-186. >>> Platelet-derived growth factor-BB; vascular endothelial growth factor 164; Saline, normal; albumin, rat serum; acetic acid; IA (femoral); IV (femoral); Rat; 2004; 28 days; Artificial kidney; controls received mp w/ vehicle; peptides; animal info (male, Fisher 344); mp attached by cannula to bioartificial hemofilter device, which surrounded and delivered agent to the femoral vessels; nephrology.
P8299 Cruze,C.A., Su,F., Limberg,B.J., Deutsch,A.J., Stoffolano,P.J., Dai,H.J., Buchanan,D.D., Yang,H.T., Terjung,R.L., Spruell,R.D., Mittelstadt,S.W., Rosenbaum,J.S. The Y2 receptor mediates increases in collateral-dependent blood flow in a model of peripheral arterial insufficiency. Peptides 2007; 28(-2-):269-280. >>> Peptide YY, recomb. human; peptide YY (3-36), recomb. human; vascular endothelial growth factor 165; PBS; glycerol; sodium citrate; Tween 20; IA (iliac); Rat; 14 days; Controls received mp w/ vehicle; replacement therapy (femoral artery occlusion); dose-response (fig. 4); half-lfie (p. 276)<30 minutes; cardiovascular; peptides; ischemia (hindlimb); animal info (male, Sprague-Dawley, 325-350 grams).
P8267 Warner-Schmidt,J.L., Duman,R.S. VEGF is an essential mediator of the neurogenic and behavioral actions of antidepressants. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2007; 104(-11-):4647-4652. >>> Vascular endothelial growth Factor 164, recomb. rat; CSF/CNS; Rat; 1003D; 3 days; Controls received mp w/ vehicle; peptides; animal info (male, Sprague-Dawley, 175-200g.).
P8163 Boodhwani,M., Mieno,S., Voisine,P., Feng,J., Sodha,N., Li,J., Sellke,F.W. High-dose atorvastatin is associated with impaired myocardial angiogenesis in response to vascular endothelial growth factor in hypercholesterolemic swine. Journal of Thoracic and Cardiovascular Surgery 2006; 132(-6-):1299-1306. >>> Vascular endothelial growth factor 165, recomb. human; Heparin; Perivascular (circumflex coronary artery); Mini-pig; 2ML4; 4 weeks; Cardiovascular; peptides; ischemia (cardiac); animal info (male, female, yucatan, 20-30 kg, 23 weeks old).
P8096 Gosain,A., Matthies,A.M., Dovi,J.V., Barbul,A., Gamelli,R.L., DiPietro,L.A. Exogenous pro-angiogenic stimuli cannot prevent physiologic vessel regression. Journal of Surgical Research 2006; 135(-2-):218-225. >>> Vascular endothelial growth factor 164, recomb.; platelet-dreived growth factor; fibroblast growth factor-2; Wound site; Mice; 2002; 11 days; Controls received mp w/ PBS; functionality of mp verified by VEGF levels in wound sponges, residual volume; stability verified by activity of residual VEGF in endothelial cell cord formation assay (fig.4); cardiovascular; peptides; animal info (female, BALB/c, 8-9 wks old, implanted sponge wounds); “The activity of VEGF isolated from the pump was comparable to fresh recombinant VEGF 164, confriming that the recombinant growth factors present in the mini-osmotic pump retain robust biological activity.” (p.221).
P8017 Kawai,T., Takagi,N., Mochizuki,N., Besshoh,S., Sakanishi,K., Nakahara,M., Takeo,S. Inhibitor of vascular endothelial growth factor receptor tyrosine kinase attenuates cellular proliferation and differentiation to mature neurons in the hippocampal dentate gyrus after transient forebrain ischemia in the adult rat. Neuroscience 2006; 141(-3-):1209-1216. >>> Vascular endothelial growth factor receptor tyrosine kinase inhibitor; DMSO; CSF/CNS (dentate gyrus); Rat; 2001; 7 days; Controls received mp w/ vehicle; dose-response (fig. 4); enzyme inhibitor (VEGF receptor tyrosine kinase); ischemia (transient forebrain); animal info (male, Wistar, 8 weeks old, carotid artery occlusion); 0.5% DMSO; agent also known as 4-[(4′-chloro-2′-fluoro) phenylamino]-6,7-dimethoxyquinazoline; tissue perfusion (dentate gyrus).
P7987 Wang,Y.M., Galvan,V., Gorostiza,O., Ataie,M., Jin,K.L., Greenberg,D.A. Vascular endothelial growth factor improves recovery of sensorimotor and cognitive deficits after focal cerebral ischemia in the rat. Brain Research 2006; 1115(–):186-193. >>> Vascular endothelial growth factor; CSF, artificial; CSF/CNS; Rat; 1003D; 3 days; Controls received mp w/ vehicle; ischemia (cerebral); behavioral study.
P7784 Gaudio,E., Barbaro,B., Alvaro,D., Glaser,S., Francis,H., Ueno,Y., Meininger,C.J., Franchitto,A., Onori,P., Marzioni,M., Taffetani,S., Fava,G., Stoica,G., Venter,J., Reichenbach,R., De Morrow,S., Summers,R., Alpini,G. Vascular endothelial growth factor stimulates rat cholangiocyte proliferation via an autocrine mechanism. Gastroenterology 2006; 130(-4-):1270-1282. >>> Vascular endothelial growth factor-A, recomb. mouse; vascular endothelial growth factor-C, recomb. mouse; Saline; BSA; IP; Rat; 1 week; Controls received mp w/ vehicle; peptides; animal info (male, Fischer 344, 150-175g.).
P7731 Carr,A.N., Howard,B.W., Yang,H.T., Eby-Wilkens,E., Loos,P., Varbanov,A., Qu,A., DeMuth,J.P., Davis,M.G., Proia,A., Terjung,R.L., Peters,K.G. Efficacy of systemic administration of SDF-1 in a model of vascular insufficiency: Support for an endothelium-dependent mechanism. Cardiovascular Research 2006; 69(-4-):925-935. >>> Vascular endothelial growth factor; stromal cell-derived factor-1a; PBS; glycerol; sodium acetate; sodium azide; IA (iliac); Rat; 2 weeks; Controls received mp w/ vehicle; dose-response (table 1); cardiovascular; peptides; animal info (adult); bilateral femoral artery ligation; occlusive cardiovascular disease.
P7561 Sun,Y.J., Jin,K.L., Childs,J.T., Xie,L., Mao,X.O., Greenberg,D.A. Vascular endothelial growth factor-B (VEGFB) stimulates neurogenesis: Evidence from knockout mice and growth factor administration. Developmental Biology 2006; 289(-2-):329-335. >>> Vascular endothelial growth factor-B; CSF, artificial; CSF/CNS; Rat; mice; 1003D; 3 days; Controls received mp w/ vehicle; ischemia (cerebral); animal info (mice, 10-12 wk old; male, Sprague-Dawley).

 

Related Publications

Dr. Penn’s Publications Listed in PubMed

Mayorga, M.E., Penn, M.S. miR-145 is differentially regulated by TGFβ1 and ischemia and targets disabled-2 expression and wnt/β-catenin activity. J Cell Mol Med, In Press (2011)

Sundararaman, S., Kiedrowski, M., Miller, T., Forudi, F., Pastore, J., Penn, M.S. Optimal SDF-1 gene transfer increases cardiac function in ischemic cardiomyopathy. Gene Therapy (In Press) 2011.

Medicetty, S., Wiktor, D., Lehman, N., Raber, A., Buakhamsri, A., Popović, Z. B., Deans, R. Ting, A.E., Penn, M.S.  Percutaneous adventitial delivery of allogeneic bone marrow derived stem cells via infarct related artery improves long-term ventricular function in acute myocardial infarction.   Cell Transplantation  (In Press) 2011.
Agarwal, U., Zhou, X., Weber, K., Dadabayev, A.R., Penn, M.S. Critical role for white blood cell NADPH oxidase mediated plasminogen activator inhibitor-1 oxidation and ventricular rupture following acute myocardial.  J Mol Cell Cardiol 50:426-32, 2011.
Mayorga, M., Dong, F., Mal, N., Jiang, Y., Howe, P.H., Penn, M.S.  Inverse relationship between paracrine and cell associated effects of cardiovascular stem cell therapy. Stem Cells Dev.  20:681-93, 2011.
Sopko N.A., Turturice B.A., Becker M.E., Brown C.R., Dong F., Popović Z.B., Penn M.S.  Bone marrow support of the heart in pressure overload is lost with aging.  PLoS One 5:e15187, 2010.
Aksoy O., Yousefzai R., Singh D., Agarwal S., O’Brien B., Griffin B.P., Kapadia S.R., Tuzcu M.E., Penn M.S., Nissen S.E., Menon V.  Cardiogenic shock in the setting of severe aortic stenosis: role for intra-aortic balloon pump support.  Heart  (In Press) 2010.

Agarwal, U., Ghalani, W., Weber, K., Zou, Y.R., Rabbany, S.Y., Rafii, S., Penn, M.S.  Role of cardiac myocyte CXCR4 expression in development and left ventricular remodeling after acute myocardial infarction. Circ Res 107:667-76, 2010. (PMC2935208)

Penn, M.S. SDF-1:CXCR4 axis is fundamental for tissue preservation and repair.  Invited Editorial Am J Pathol  177:2166-8, 2010.

Wang K., Zhou X., Huang Y., Khalil M., Wiktor D., van Giezen J.J., Penn M.S.  Adjunctive treatment with ticagrelor, but not clopidogrel, added to tPA enables sustained coronary artery recanalisation with recovery of myocardium perfusion in a canine coronary thrombosis model.  Thromb Haemost 104:609-17, 2010
Willerson J.T., Perin E.C., Ellis S.G., Pepine C.J., Henry T.D., Zhao D.X., Lai D., Penn M.S., Byrne B.J., Silva G., Gee A., Traverse J.H., Hatzopoulos A.K., Forder J.R., Martin D., Kronenberg M., Taylor D.A., Cogle C.R., Baraniuk S., Westbrook L., Sayre S.L., Vojvodic R.W., Gordon D.J., Skarlatos S.I., Moyé L.A., Simari R.D.; Cardiovascular Cell Therapy Research Network (CCTRN).   Intramyocardial injection of autologous bone marrow mononuclear cells for patients with chronic ischemic heart disease and left ventricular dysfunction (First Mononuclear Cells injected in the US [FOCUS]): Rationale and design.  Am Heart J  160:215-23, 2010
Rabbany, S.Y., Pastore, J. Yamamoto, M., Miller, T., Rafii, S., Aras, R., Penn, M.  Continuous delivery of stromal cell-derived factor-1 from alginate scaffolds accelerates wound healing.  Cell Transplantation 19:399-408, 2010.

Dong, F., Khalil, M., Kiedrowski, M. Zhou, X., Penn, M.S. Critical role for leukocyte hypoxia inducible factor-1α expression in post-MI left ventricular remodeling.  Circ Res 106:601-10, 2010.

Penn M.S., Agarwal U. IGF-1 and mechanisms of myocardial repair. Invited Editorial Int J Cardiol 7;138(1):1-2, 2010.
Penn, M.S., Mayorga, M.E. Searching for understanding with the cellular lining of life.  Invited Editorial  Circ. Res. 106:1554-6, 2010. (PMC2753196)
Reviews and Book Chapters

Penn, M.S., Bakken, E.E.  Heart-Brain medicine: update 2009.  Cleve Clin J Med.  77  Suppl 3:S4-6, 2010.

Pozuelo, L., Tesar, G., Zhang, J., Penn, M., Franco, K., Jiang, W. Depression and heart disease: what do we know, and where are we headed.  Cleve Clin J Med. 76:59-70, 2009
Penn, M.S., Bakken, E.E.  Heart-brain medicine: Update 2008. Cleve Clin J Med. 76 Suppl 2:S5-7, 2009.
Mayorga, M., Finan, A., Penn, M. Pre-transplantation Specification of Stem Cells to Cardiac Lineage for Regeneration of Cardiac Tissue.  Stem Cell Rev Rep. 5:51-60, 2009.
Goel SS, Harvey JE, Penn M, Menon V.  Images in cardiovascular medicine. Left anterior descending coronary artery occlusion secondary to blunt chest trauma. Circulation. 119:1975-6, 2009.
Sherman W, Dimmeler S, Hare JM, Penn M. Cardiovascular repair and regeneration 2008: the fourth International Conference on Cell Therapy for Cardiovascular Disease (IC3D).  EuroIntervention 4:47-9, 2008.
Penn, M.S., Bakken, E.E.  Heart-Brain medicine: Update 2008.  Cleve Clin J Med. 76 Suppl 2:S5-7, 2009.
Penn, M.S., Khalil, M. Exploiting stem cell homing for gene delivery.  Expert Opinions in Biotechnology Expert Opin Biol Ther. 8:17-30, 2008.
Shpargel, K.B., Jalabi, W., Jin, Y., Dadabayev, A., Penn, M.S., Trapp, B.D.  Preconditioning paradigms and pathways in the brain.  Cleve Clin J Med. 75 Suppl 2:S77-82, 2008.
Penn, M.S., Mangi, A.A., Genetic Enhancement of Stem Cell Engraftment, Survival and Efficacy.  Circ Res, 102:1471-82, 2008.
Penn, M.S., Bakken, E.E.  Heart-brain medicine: update 2007.  Cleve Clin J Med. 75 Suppl 2:S3-4, 2008.
Penn, M.S., The role of leukocyte-generated oxidants in left ventricular remodeling.  Am J Cardiol. 101:30D-33D, 2008.
Penn, M.S., Bakken, EE.  Heart-brain medicine: where we go from here and why.  Cleve Clin J Med. 74 Suppl 1:S4-6, 2007.
Penn, M.S., Mal, N. Stem cells in cardiovascular disease: methods and protocols.  Methods Mol Med. 2006;129:329-51.
Penn, M.S. Stem-cell therapy after acute myocardial infarction: the focus should be on those at risk. Invited Editorial Lancet. 367:87-8, 2006

 

Electrical stimulation of muscle progenitor cells – Repository …
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ADIPOSE STEM CELL DIFFERENTIATION TOWARDS VASCULAR LINEAGES USING NOVEL 3D ELECTRICAL STIMULATION SYSTEM

Presenter: Authors:

Miina Bjorninen, MSC
Bjorninen M, Gilmore K, Pelto J, Kellomaki M, Miettinen S, Wallace G, Grijpma D, Haimi S

BioMediTech University of Tampere

Electrical stimulation (ES) has potential for the directed differentiation of human adipose stem cells (hASCs) towards desired lineages in the presence or absence of chemical induction. To date, reusable in vitro electrical stimulation devices that can stimulate several cell constructs simultaneously are unavailable commercially. We therefore developed a system that could electrically stimulate cells reliably and repeatably. Conductive polypyrrole (PPy) coatings on poly (trimethylene carbonate) (PTMC) scaffolds were tested for smooth muscle cell (SMC) and endothelial cell (EC) differentiation of human ASCs with and without ES.

In the first part of the study PTMC scaffolds were chemically coated with PPy in the presence of hyaluronic acid (HA) and their effects on SMC and EC differentiation of hASCs was studied. In the second part of the study, pulsed biphasic electric current (BEC) was applied through the hASC-seeded PPy-coated constructs using a novel in-house ES electrodes composed of titanium nitride (TiN) coated metallic titanium. BEC was applied under SMC differentiation conditions with pulse widths of 0.25 and 1 ms. Cells were characterized for their attachment, viability, cell number as well as EC and SMC marker expression via immunofluorescence staining.

PPy-coated scaffolds provided stronger cell attachment, induced higher proliferation as well as stronger SMC and EC marker expression for hASCs, compared to uncoated PTMC scaffolds under both differentiation conditions. Cells on both scaffold types showed similar viability. Cells under BEC with 1 ms pulse width showed similar viability to controls whereas with 0.25 ms pulse width viability was reduced after 14 days of BEC. Similarly, cells undergoing BEC with 1 ms pulse width showed similar marker expression as that of controls whereas 0.25 ms pulse width showed lower expression levels.

In conclusion, the novel ES electrodes were found to be suitable for delivering BEC for hASCs and can be recommended for in vitro use due to their stability and reliability with repeated use. PPy coating promoted hASC attachment, proliferation and SMC and EC marker expression. The novel electrical stimulation system therefore has potential for vascular tissue engineering applications.

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Bioelectric Properties of Myogenic Progenitor Cells

https://www.liebertpub.com/doi/pdfplus/10.1089/bioe.2018.0002

BIOELECTRICITY
Volume 1, Number 1X, 2018 a Mary Ann Liebert, Inc. DOI: 10.1089/bioe.2018.0002
Review Article
Bioelectric Properties of Myogenic Progenitor Cells
Colin Fennelly, MS,1 and Shay Soker, PhD2,3
Abstract
Modern stem cell research has mainly focused on protein expression and transcriptional networks. However, transmembrane voltage gradients generated by ion channels and transporters have demonstrated to be powerful regulators of cellular processes. These physiological cues exert influence on cell behaviors ranging from differentiation and proliferation to migration and polarity. Bioelectric signaling is a fundamental element of living systems and an untapped reservoir for new discoveries. Dissecting these mechanisms will allow for novel methods of controlling cell fate and open up new opportunities in biomedicine. This review focuses on the role of ion channels and the resting membrane potential in the proliferation and differentiation of skeletal muscle progenitor cells. In addition, findings relevant to this topic are presented and potential implications for tissue engineering and regenerative medicine are discussed.
Keywords: differentiation, skeletal muscle, stem cells, bioelectricity
Introduction
All cells segregate charges across the plasma mem- brane to generate and maintain the resting membrane potential (Vmem). These steady-state electrochemical ion fluxes occur through channel and pump proteins in non- excitable cells and are being increasingly recognized as im- portant players in cellular processes, including proliferation and differentiation.1–4 These signals are highly dynamic and are not as easily detected by conventional molecular biology techniques. For example, during Xenopus embryogenesis, left–right patterning is established by a voltage gradient that leads to electrophoretic movement of small molecule mor- phogens through gap junction complexes.5–8 This event could not be regulated by RNA interference or other knockdown approaches since it involves maternal proteins and occurs hours before zygotic transcription begins.6 Additional com- plexity is added by the fact that physiological parameters such as Vmem and pH can be altered through the actions of dif- ferent translocator proteins. This means that cells can reach different bioelectric states with the same protein expression profiles and the same bioelectric state through different ion fluxes or the same ion fluxes from different channels.9 This concept has been demonstrated before, wherein misexpres- sion of a heterologous yeast proton pump was able to rescue vertebrate regeneration that is normally initiated by a V- ATPase in the tadpole tail.10 The yeast gene encoded for a protein that had no sequence or structure homology to the V-
ATPase. This proved that proton pumping was required to trigger the regeneration process when the native V-ATPase gene was blocked and that this was not dependent on a nonion passing function such as protein scaffolding. These examples highlight the importance of physiological parameters and limitations of the current gene expression-centered para- digm. Fortunately, approaches involving drug screens can be utilized to dissect the ways membrane voltage potentials transduce into cellular signaling pathways.11,12 In addition, voltage-sensitive fluorescent dyes that have been developed can be used to visualize membrane potential gradients non- invasively and in real time.13–16 These tools can be coupled with molecular biology techniques and pharmacological agents targeting ion channels to further interrogate the role of Vmem in stem cell biology. Although biological electricity is a relatively arcane topic and an unconventional perspective for cell biologists,17 it has a long history going all the way back to the 1700s.2,3,6,18–37 Recent advancements have re- vealed key roles for this type of signaling on various scales, including (1) signaling at the plasma membrane,38,39 (2) proliferation and differentiation at the single cell level,1,6 (3) cell migration at the multicellular tissue level,2,3,40,41 (4) large scale regeneration of complex structures, and (5) organ for- mation during embryonic development.17,42–44
In vivo, cells are immersed in a rich environment of both biophysical and biochemical stimuli from intracellular and extracellular sources that directly influence cellular pro- cesses. Myogenic progenitor cells (MPCs) are also referred

page1image2180125776

1Department of Neuroscience, Novartis Institutes for BioMedical Research, Inc., Cambridge, Massachusetts. 2Wake Forest Institute for Regenerative Medicine, Winston-Salem, North Carolina.
3Wake Forest School of Medicine, Winston-Salem, North Carolina.
29
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30
FENNELLY AND SOKER
to as satellite cells due to their location between the basal lamina and muscle fibers.45 They reside in a quiescent state until they are activated during tissue repair, where progenitor cells initially proliferate to expand their numbers.46 A sub- population of newly generated MPCs begins to fuse into myotubes and organize into myofibers to replace damaged tissue, and a subpopulation of MPCs also return to a quies- cence state at their native niche on the muscle fiber for future repairs.47 Previous studies have revealed the importance of the microenvironment and its ability to transduce into sig- naling pathways that affect MPCs’ ability to engage in tissue repair.48–56 Removal of satellite cells from their endogenous niche has given rise to challenges maintaining stem cell properties during in vitro expansion.57–59 The ability to ex- ecute temporal control over cell fate in vitro will be para- mount for future developments in tissue engineering and cell therapy. This review focuses on ion channels and trans- membrane voltage gradients (Vmem) at the cellular level and their impact on the proliferation and differentiation of skel- etal muscle stem/progenitor cells. The differentiation process of MPCs has been well characterized and involves various signaling pathways and molecular effectors.46,60–64 Strate- gies involving pharmacological agents targeting ion trans- locator proteins and molecular biology techniques have revealed an indispensible role for a specific potassium channel and cellular Vmem in the early stages of MPC dif- ferentiation. These discoveries directly link this parameter with other signaling pathways as well as expression of myo- genic differentiation genes.65 These findings highlight the synergy between biophysical and biochemical signaling and taken together warrant a paradigm shift in stem cell biology to be more inclusive of physiological parameters such as Vmem and its involvement in cell growth and differentiation.
Ion Channels, Transmembrane Voltage Gradients, and Muscle Progenitor Cell Proliferation
Various channel and pump proteins segregate ions across the lipid bilayer to establish the cellular resting potential (Vmem). These transmembrane voltage gradients are steady- state cues that act on longer time scales than the action potentials of excitable cells and can also serve as a cell au- tonomous bioelectric signal.1,4,6,11,17 Vmem has long been recognized as a key regulator of cellular states. Cellular Vmem levels vary widely among different cell types (-10 to -90 mV) and this parameter generally corresponds to pro- liferative potential.6,66 This trend is thought to be functional since mitotically active cells such as embryonic, cancer, and stem cells have shown to be more depolarized (0 to -30 mV) than terminally differentiated cells (-50 to -100 mV) that no longer proliferate.66 Mammalian liver cells reside more to- ward the middle of the scale and it has been suggested that this is correlated with the extraordinary regenerative capacity of this organ.67 These initial observations implied that Vmem (or other biophysical parameters) could be a targetable con- trol node that can be leveraged to direct stem cell behavior toward desired outcomes in a biomedical setting. Clarence D. Cone Jr. hypothesized that there was a relationship between Vmem and cell growth.68–70 He even produced his own theory on the connection between electrical membrane po- tentials and mitotic control.71,72 Since then, Vmem has pro- ven to exert a strong influence on cellular proliferation in
various cell types.1,4 Studies have demonstrated that artificial perturbation of Vmem can result in transcriptional changes of cell cycle regulators, including cyclin E and p27 and tran- scription factors c-myc and c-fos.73,74 Other investigations have noted changes in ion channel expression throughout cell cycle phase progression.75–92
Proliferating MPCs are known to express tetrodotoxin- resistant voltage-gated sodium currents and calcium- activated potassium currents that increased 10-fold with proliferation in vitro.93 Tetrodotoxin-resistant sodium cur- rents were also observed in the mouse C2C12 cell line along with calcium-activated potassium channels, an ATP-induced slow potassium current, an inward rectifier potassium cur- rent, and a volume-induced chloride current.94There is no data to suggest whether or not these currents are directly involved in cell cycle progression of MPCs or simply related to ‘‘housekeeping’’ processes, but it is known that satellite cells (proliferative stage) are measured to have a Vmem around -10 mV and myotubes (nonproliferating, withdrawn from the cell cycle) are around -70 mV.95,96 These data are consistent with the previous observations made in other cell types and suggest a concomitant relationship between Vmem and MPC proliferation.66 More recent investigations have shown that sustained depolarization can regulate MPC growth in a biphasic manner.97 Our data showed that expo- sure to extracellular potassium or ouabain was able to stim- ulate growth and increase the number of cells in S phase.97 However, further increasing concentrations of extracellular potassium decreased cell growth, the number of cells in S phase, and drove cells into G1 in a dose-dependent manner.97 Depolarization through exposure to extracellular barium or potassium has also induced a biphasic effect on growth in neural progenitor cells.98 In addition, cell cycle arrest at G1 in response to depolarization has been seen in kidney cells,99lymphocytes,100 Schwann,89 and glial cells.101,102 For the latter, depolarization-induced growth inhibition was noted to result in accumulation of cyclin-dependent kinase inhibitors p27(Kip1) and p21(CIP1).102
Interestingly, depolarization has also been shown to induce cell proliferation in mouse macrophages and neonatal car- diomyocytes, and even re-enter mature neurons into the cell cycle.74,103–105 It is possible that there is an optimum voltage range for proliferation, and pushing cells outside of this window in one direction (depolarized or hyperpolarized) can drive cells to quiescence or induce cell cycle entry. It has been proposed that there are rhythmic oscillations between different Vmem values throughout the cell cycle wherein cells are mostly depolarized during G1, experience a spike in hyperpolarization before S phase, and depolarize again for a prolonged period during mitosis.1,70,84,85,106,107 This model would imply that artificial depolarization could prevent S phase induction by blocking the hyperpolarization step. Further complication is added by the fact that cells do not necessarily have only one overall Vmem value, but may possess different voltage potentials across separate domains of their entire surface.1,43,108,109Physiological parameters such as Vmem arise from the cumulative activity of the dif- ferent ion channels expressed on the cell membrane. It is also important to note that these signals can result from the charge gradient alone (bioelectric signal encoded in Vmem change) or result from the flow of individual ion species (K+, Na+, H+, or Cl-).11 More research to further elucidate the roles of ion
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MPC BIOELECTRICITY
31
channels and bioelectric signaling in the proliferation of MPCs will provide exciting opportunities for controlling cell fate in the context of cell therapies, tissue engineering, and regenerative medicine.
The Role of the Resting Membrane Potential
in the Differentiation of Muscle Progenitor Cells
Understanding how biophysical and biochemical signals coordinate and govern cell properties will allow for the de- velopment of novel methods for directing stem cell behavior toward therapeutic goals. The observed difference between depolarized cells that are mitotically active and differentiated cells that are hyperpolarized inspired investigations into this relationship. Recent studies have revealed that electrophys- iological changes accompany cell differentiation in a variety of different cell types.4 Changes in the expression of ion channel proteins throughout differentiation are known to occur in neural,110 endothelial,111 human mesenchymal stem cells,112,113 and various other cell types.4,114–123 Moreover, perturbations in Vmem have proven to regulate the differ- entiation process, demonstrating that this parameter is not simply a reflection of cell status, but rather an instructive parameter that can be used to control progenitor cells.124,125 Vmem has been identified as an integral player in MPC dif- ferentiation (Fig. 1). MPCs from different species experience Vmem changes from about -10 mV to a range between -55 and -70 mV for myotubes.93,126–128 For human MPCs, this process involves expression of an ether-a‘-go-go (EAG) po- tassium current that initially hyperpolarizes cells to -32 mV, generating cells that are fusion competent.95 Then, before cell fusion, an inward rectifier potassium channel (Kir2.1) hy- perpolarizes the Vmem to around -65 mV.95,129 These cur- rents are different from the voltage-gated sodium and calcium-activated potassium currents exclusively expressed in proliferating satellite cells, which indicate specific roles for different ion channels during different stages of MPC dif- ferentiation.93 Inward rectifier potassium currents have been recognized in mature muscle fibers and are known to con- tribute to the maintenance of Vmem and myofiber excit- ability.130 Interestingly, inward rectifier potassium currents have also been observed in the differentiation of hemato- poetic progenitor cells as well, suggesting that this prereq- uisite for differentiation might be part of a conserved or similar mechanism across different cell types and potentially have functions independent of regulating Vmem for excitable tissues.131 The chloride channel Clc-1 contributes to the stabilization of Vmem in adult skeletal muscle, and mutations in this gene have proven to be correlated with muscular disease.132 This gene was also noted to be reflective of the developmental stages of myoblasts. Clc-1 mRNA was orders of magnitudes lower in myoblasts and C2C12 cells than in adult skeletal muscle and C2C12-derived myotubes.133
Vmem has been directly linked to second messenger cal- cium signaling, which is essential for cell fusion.134 More specifically, Kir 2.1-associated MPC hyperpolarization sets the stage for sustained calcium influx through T-type Ca2+ channels.134 One of the unique features of this signaling is that the steady-state calcium signaling is able to be achieved at a specific voltage range (-40 to -80mV), wherein an equilibrium exists between the open, closed, and inactivated status of the T-type Ca2+ channels (termed window current,
maximum activity at -58mV).134 This perpetual cycle ro- tates between these states in a continuum and allows for a small fraction of channels to remain open and gives rise to sustained low amplitude calcium spikes.134 Furthermore, it was demonstrated that targeting delayed rectifier potassium currents with antiarrhythmic agents to modulate Vmem (depolarization at a specific window domain) could be used to trigger a rise in intracellular calcium and accelerate MPC fusion.135 This was the first experiment that highlighted the key role of Vmem as an instructional parameter related to MPC differentiation and demonstrated that it can be targeted to influence MPC behavior.
Follow-up studies reported that Kir2.1 was required to in- duce hyperpolarization that precedes the expression of myo- genic transcription factors myogenin and mef2.136 Pharmacological blockade of this channel or knockdown of the gene also inhibited cell fusion and expression of both differentiation genes.65,136 In addition to activation of dif- ferentiation genes, this signaling event was found to initiate the differentiation process specifically through the calci- neurin pathway.65 Depolarization with extracellular potas- sium was able to block expression of these factors and blunt calcineurin signaling.65 In addition to regulating expression of myogenic differentiation genes, our efforts have shown that depolarization with extracellular potassium can attenuate cell fusion and myotube formation as well as maintain ex- pression of muscle stem cell marker Pax7.97Furthermore, these inhibitions (cell fusion and expression of myogenic differentiation markers) in both studies were transient and when cells were returned to control conditions, the differen- tiation process resumed to completion. Taken together, these discoveries reveal that Vmem modulations can act upstream of and influence downstream processes that ultimately impact MPC fusion and expression of differentiation genes related to myogenesis. These results also demonstrate that artificial modulation of electrochemical ion gradients can exert control over MPC differentiation pathways and promote expression of stem cell marker Pax7.97 This has attractive implications for in vitro expansion of cultures for tissue engineering or cell therapy efforts that require large number of functional MPCs that need to retain their progenitor properties.63,137,138
MPC differentiation involves additional players upstream of Kir2.1 activity. The transmembrane endoplasmic reticulum calcium sensor stromal interacting molecule 1 and calcium channel Orai1 have been shown to activate store-operated calcium entry, and silencing these genes leads to impaired cell fusion and thwarts membrane hyperpolarization.139 The nonvoltage-gated transient receptor potential canonical chan- nel (TRPC) plays a crucial role in the fusion process.140 Human primary myoblasts express various isoforms of this nonselec- tive cation channel, including TRPC1, TRPC3, TRPC4, and TRPC6. TRPC1 and TRPC4 mediate Ca2+ influx and silencing these genes significantly reduced MEF2 positive cells and decreased both myotube width and number of nuclei per myotube.140 One unique aspect of the MPC differentiation process is that Kir2.1 hyperpolarization is switched on by de- phosphorylation of tyrosine residue 242.141 Interestingly, Kir 2.1 channels are expressed and phosphorylated at tyrosine 242 in proliferating MPCs, indicating that this channel lies dormant at the cell membrane until acted on by phosphatase activity.141 In addition to post-translational modifications,141–145 studies have suggested that signaling pathways such as Ras-MAPK
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32 FENNELLY AND SOKER

page4image2175799360

FIG. 1. Differentiation of skeletal muscle stem cells and the physiological state space hypothesis: The physiological state space hypothesis proposes that cells can be characterized by their physiological properties and visualized along axes corresponding to these parameters. Vmem and intracellular potassium are depicted above, but other orthogonal axes can include intracellular pH, sodium, or chloride content (solid black lines). This paradigm can be used to visualize the timeline for MPC differentiation (dotted black lines) including the key events involved. The expression profile at different stages of this progression is depicted to the right (green, orange, and red boxes). MPC, myogenic progenitor cell.
could regulate Kir 2.1 trafficking,146 anchoring proteins can aid in Kir 2.1 channel stability at the membrane,147–149 and gating properties of these channels can be influenced by PIP2 bind- ing.150–153 These examples along with others154–159 represent the complex interplay that can potentially exist between bio- physical and biochemical signals and illuminate the impor- tance for understanding how they synchronize to orchestrate cell behavior.
Voltage gradients have been shown to orient cells during mitosis,160,161 establish cell polarity,2,7 and activate signaling molecules at the plasma membrane38,39,41 It has been pro- posed that the role of Vmem in cell fusion can involve pro- teins that are needed for cell–cell interactions such as cell adhesion molecules, connexins, and gap junctions.95,162–165 Gap junctions have been previously implicated in MPC dif- ferentiation.164,166–169 C2C12 myoblasts were shown to in- crease expression of both myogenin and cx43 when exposed to extremely low-frequency electromagnetic fields.170 In addition, blocking gap junctions have shown to inhibit myogenin expression.171 In our cell culture system, MPCs begin to fuse when cultures reach confluency, suggesting that cell–cell contact has an important role in the fusion process. Considering that MPCs are located directly on myofibers in vivo, differences in cytoplasmic voltage gradients between
myotubes and MPCs could potentially mobilize signaling molecules through gap junction proteins. It is also possible that the Vmem changes can alter cell orientation that would promote the fusion process. Future efforts will need to con- sider the role of biophysical interactions in MPC fusion, and these findings will shed further light on the relevance of bioelectric signaling.
Opportunities for Regenerative Medicine and Tissue Engineering
Emerging evidence increasingly advocates the notion that modulation of bioelectric properties such as cellular Vmem can be utilized to guide cells toward desired behaviors for thera- peutic purposes in vitro (tissue engineering) and in vivo (re- generative medicine).17 Instructional bioelectric cues encoded in steady-state Vmem changes at the plasma membrane are only one component of the morphogenetic field: a system of physiological, mechanical, and genetic properties of cells and tissues that is proposed to store all the information to ultimately orchestrate anatomical development during morphogenesis and maintains large scale patterning during morphostasis.44 Bioelectric signals have demonstrated to be functional deter- minants of cell behavior through control of cell cycle phase
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MPC BIOELECTRICITY
33
progression and differentiation.1,4,6 One attractive feature of bioelectric signaling is its ability to act as a master regulator on a large scale that triggers regeneration of complex structures in vivo from simple binary input signals (hyperpolarization or depolarization).6,17 For example, Vmem changes can rejuve- nate tail regeneration in Xenopus and have also been shown to program (and reprogram) head–tail regeneration in the blas- tema of planaria flatworms.10,172 Moreover, the diverse and universal expression of ion channels makes them favorable candidates for biomedical intervention. Regenerative medicine aims to harness the endogenous repair mechanism already embedded within the body and decoding this communication system will unleash opportunities for major advancements in biomedicine.173 This challenging task will require the mapping of both spatial and temporal aspects of regulated ion fluxes and their resulting outcomes on individual cell behaviors and tissue regeneration.173
This growing body of literature has included development of the physiological state space hypothesis.6,9,67 It has been suggested that cell types cluster in specific states along or- thogonal axes corresponding to physiological parameters such as Vmem, intracellular sodium content, potassium content, chloride content, and internal pH. Modulation of these pa- rameters would drive cells into different regions of this space and alter cell status such as proliferative versus quiescent or differentiated versus progenitor cell. Just as pH changes acti- vate degradative proteins in the lysosome, there exist mech- anisms that respond to physiological changes in the intracellular environment.11 For example, a sodium current has been recognized as playing an essential role in Xenopus tail regeneration and this leads to downstream activity of a salt-inducible kinase.174 This paradigm can be applied spe- cifically to MPCs given the instrumental role Vmem plays in differentiation (Fig. 1). The physiological state space concept could additionally be extended to serve as a potentially ef- fective strategy for demarcating cells that have certain prop- erties that correspond to progenitor or proliferative status.
Although there are not many investigations into this topic, the works covered in this review demonstrate that MPC fate can indeed be controlled through Vmem modulations in vitro (Table 1). Vmem depolarization through pharmacological blockade of Kir2.1 or modulation of extracellular potassium levels in the culture medium was able to block calcineurin activation and expression of myogenic differentiation genes.65,136 This is consistent with more recent studies wherein sustained depolarization has proven to enact tran- sient control over cell fusion and maintain expression of muscle stem cell marker Pax7.57,97 Moreover, exposure to increasing concentrations of extracellular potassium regu- lated MPC proliferation and cell cycle phase progression in a biphasic and dose-dependent manner.97 An exciting aspect of these findings is that they demonstrate Vmem is a singular and targetable parameter that can be modulated to regulate MPC growth and differentiation in vitro through simple manipulation of culture medium. The dose-dependent aspect hints at an ability to fine tune cellular responses to artificial perturbations of Vmem. The biphasic influence on growth suggests a voltage range specific for cellular status. A voltage window that initiates Ca2+ signaling required to advance MPC differentiation has already been identified and it is possible there could be similar mechanisms that are involved in cell cycle progression.134 Other similar investigations have
revealed the ability for Vmem to act as a control switch for
differentiation and regulate cell growth in different cell types.1,4,73,102,105,124,125,175–178
Cell therapy requires a large number of functional cells and in vitro expansion is currently the most convenient way.179–181 This means that the expanded cells would need to maintain their myogenic properties (ability to engraft within the host, uptake the satellite cell niche, and fuse with endogenous MPCs), while avoiding differentiation in culture. Our prior efforts have shown that an in vitro cell culture system in- volving myogenic culture medium replete with growth factors and extracellular matrix substratum can promote long-term MPC expansion and retain self-renewal and in vivo en- graftment capabilities.179 Enhancing tissue culture medium with small molecules or cytokines to alter cell phenotypes has also shown to be successful.182,183Satellite cells have been shown to hold a large degree of heterogeneity in terms of gene expression,64 and cell therapy efforts have faced challenges identifying cell populations that are most likely to integrate into the stem cell niche and aid in tissue regeneration.57,62,184,185 Characterizing MPCs in terms of their physiological parameters, and coupling this with the molecular signatures such as cell surface markers, could lead to the identification of new popu- lations that will perform better during cell therapy. Pharma- ceuticals targeting endogenous transporters already approved for use in humans and ectopic expression of well-characterized transporters with gene therapy could be used to influence cell behavior and augment the regenerative process in defective or diseased tissues.186,187 Furthermore, perturbation of physiolog- ical states pharmacologically or genetically, in conjunction with strategies that have been previously deployed such as coinject- ing cells with signaling modulators or growth factors, may lead to more successful outcomes.188,189
Conclusion
The genetic signatures and molecular machinery involved in MPC proliferation and differentiation have been exten- sively characterized. However, the resting membrane poten- tial (Vmem) has proven to be an instructional parameter that regulates MPC proliferation and differentiation in vitro. Ar- tificial modulations of cellular Vmem have demonstrated an ability to exert control over MPC growth and fusion as well as expression of stem cell marker Pax7 and differentiation genes myogenin and mef2. These findings illustrate that bioelectric signals are important elements influencing MPC behavior and can be used as a tool to dictate cell fate for tissue engineering in vitro and potentially in vivo. Future advancements will unlock the true potential of biophysical signaling and open up new opportunities in regenerative biomedicine.
Glossary
Bioelectricity: long-term and steady-state ion flows that establish electric fields and voltage gradients across the cell membrane within living systems that serve as in- structional cues in addition to their basic housekeeping functions.17,67
Bioelectric signal: A signal that is encoded in the charge gradient across the cell membrane (Vmem) and not de- fined by the movement of specific ions or activity of specific channels or pumps. The activity of different ion channels or the movement of different ion species can
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34 FENNELLY AND SOKER
Table 1. Regulating Myogenic Progenitor Cell Behavior by Targeting Cellular Vmem
Agent(s) used
Bioelectric modulation
Cellular outcome
Reference
Methanesulfonanilide class III antiarrhythmic agents,
genetic knockdown
Depolarization by inhibition of EAG K+channels
Accelerate fusion
119
Tyrosine kinase inhibitor genistein
Increase Kir 2.1 activity
124
Extracellular K+, ouabain
Depolarization
Attenuate fusion
52
Mibefradil, Cs+
Blocking Kir 2.1 activity
118
RNA knockdown of Kir 2.1
Extracellular K+
Depolarization
Biphasic influence on growth: impede cell growth and drive cells into G1 stimulate growth and increase number of cells in S phase
52
Extracellular K+, ouabain
Ouabain, extracellular K+
Depolarization
Maintain expression of stem cell marker Pax7
52
Extracellular K+
Depolarization
Prevent expression of myogenin and Mef2
120
Cs+, mibefradil
Blocking Kir 2.1 activity
51
EAG, ether-a`-go-go.
generate the same bioelectric signals as long as the re- sulting Vmem achieved is the same (potassium efflux from inside the cell to outside the cell and chloride influx from outside the cell to the intracellular space both make the cell more negative/hyperpolarized).11
  •  Bioelectric state/physiological state: Cellular status that is defined by physiological parameters such as the content of specific ion species within the cell or Vmem.6,9,67 Characterizing cells through this lens will allow for certain cell types to cluster in the same re- gions along orthogonal axes and can be used to define cells in terms of these properties.
  •  EAG: Ether-a`-go-go K+ current. A noninactivating delayed rectifier K+ current.
  •  Ion translocator: Channel, pump, or gap junction protein that allows charged molecules to move pas- sively across the cell membrane or use energy to ac- tively transport ions against the concentration gradient.
  •  Kir 2.1: Inward rectifying potassium channel. Ion channel gene KCNJ2.
  •  Mef2: Myocyte enhancer factor 2. Myogenic differen- tiation marker.
  •  Morphogenesis/morphostasis: During embryonic de- velopment, a living organism establishes its anatomy (morphogenesis), and throughout its adult lifespan, the organism maintains its shape (morphostasis) against normal wear and tear (cell turnover and/or aging) or damage (regeneration).44
  •  MPC: Myogenic/muscle progenitor cell. Also referred to as satellite cell or skeletal muscle stem cell.
  •  MyoD: Myogenic differentiation 1. Mid differentiation myogenic marker.
  •  Pax7: Paired box gene 7. A transcription factor that is a marker for satellite/skeletal muscle stem cells (MPCs).190–193
Vmem: The cellular resting membrane potential as de- fined by the charge gradient across the lipid bilayer membrane that is measured in millivolts and results from the ion concentrations inside and outside of cells.
Acknowledgment
We would like to thank Crossland Designs Inc. for assis- tance with the visuals of Figure 1.
Author Disclosure Statement
No competing financial interests exist.
References
1. Blackiston DJ, McLaughlin KA, Levin M. Bioelectric controls of cell proliferation: Ion channels, membrane voltage, and the cell cycle. Cell Cycle 2009;8:3519–3528.
2. McCaig CD, Rajnicek AM, Song B, et al. Controlling cell behavior electrically: Current views and future potential. Physiol Rev 2005;85:943–978.
3. McCaig CD, Song B, Rajnicek AM. Electrical dimensions in cell science. J Cell Sci 2009;122:4267–4276.
4. Sundelacruz S, Levin M, Kaplan DL. Role of membrane potential in the regulation of cell proliferation and dif- ferentiation. Stem Cell Rev 2009;5:231–246.
5. Levin M, Thorlin T, Robinson KR, et al. Asymmetries in H+/K+-ATPase and cell membrane potentials comprise a very early step in left–right patterning. Cell 2002;111:77–89.
6. Levin M, Stevenson CG. Regulation of cell behavior and tissue patterning by bioelectrical signals: Challenges and opportunities for biomedical engineering. Annu Rev Biomed Eng 2012;14:295–323.
7. Levin M. Is the early left-right axis like a plant, a kidney, or a neuron? The integration of physiological signals in embryonic asymmetry. Birth Defects Res C Embryo To- day 2006;78:191–223.
Downloaded by 24.11.114.253 from www.liebertpub.com at 02/10/19. For personal use only.
MPC BIOELECTRICITY 35
  1. Levin M, Palmer AR. Left–right patterning from the in- side out: Widespread evidence for intracellular control. Bioessays 2007;29:271–287.
  2. Levin M. Bioelectric mechanisms in regeneration: Unique aspects and future perspectives. Semin Cell Dev Biol 2009;20:543–556.
  3. Adams DS, Masi A, Levin M. H+ pump-dependent changes in membrane voltage are an early mechanism necessary and sufficient to induce Xenopus tail regeneration. Develop- ment 2007;134:1323–1335.
  4. Adams DS, Levin M. Endogenous voltage gradients as mediators of cell-cell communication: Strategies for in- vestigating bioelectrical signals during pattern formation. Cell Tissue Res 2013;352:95–122.
  5. Adams DS, Levin M. Inverse drug screens: A rapid and inexpensive method for implicating molecular targets. Genesis 2006;44:530–540.
  6. Adams DS, Levin M. General principles for measuring resting membrane potential and ion concentration using fluorescent bioelectricity reporters. Cold Spring Harb Protoc 2012;2012:385–397.
  7. Oviedo NJ, Nicolas CL, Adams DS, et al. Live imaging of planarian membrane potential using DiBAC4(3). CSH Protoc 2008;2008:pdb.prot5055.
  8. Adams DS, Levin M. Measuring resting membrane potential using the fluorescent voltage reporters DiBAC4(3) and CC2- DMPE. Cold Spring Harb Protoc 2012;2012:459–464.
30. Woodruff R, Telfer W. Electrophoresis of proteins in in- tercellular bridges. Nature 1980;286:84–86.
31. Borgens RB. What is the role of naturally produced electric current in vertebrate regeneration and healing. Int Rev Cytol 1982;76:245–298.
32. Borgens RB, Robinson KR, Vanable J, et al. Electric Fields in Vertebrate Repair: Natural and Applied Voltages in Vertebrate Regeneration and Healing. New York: Alan R Liss, 1989.
33. Nuccitelli R. Endogenous ionic currents and DC electric- fields in multicellular animal tissues. Bioelectromagnetics 1992;13:147–157.
34. Hotary KB, Robinson KR. Evidence of a role for endog- enous electrical fields in chick embryo development. Development 1992;114:985–996.
35. Hotary KB, Robinson KR. Endogenous electrical currents and voltage gradients in Xenopus embryos and the conse- quences of their disruption. Dev Biol 1994;166:789–800.
36. Altizer A, Moriarty L, Bell S, et al. Endogenous electric current is associated with normal development of the vertebrate limb. Dev Dyn 2001;221:391–401.
37. Kloth LC. Electrical stimulation for wound healing: A review of evidence from in vitro studies, animal experi- ments, and clinical trials. Int J Low Extrem Wounds 2005; 4:23–44.
38. Olivotto M, Arcangeli A, Carla` M, et al. Electric fields at the plasma membrane level: A neglected element in the mechanisms of cell signalling. Bioessays 1996;18:495–
16. Vandenberg LN, Morrie RD, Adams DS. V-ATPase-
dependent ectodermal voltage and pH regionalization are 504.
required for craniofacial morphogenesis. Dev Dyn 2011;
240:1889–1904.
  1. Levin M. Molecular bioelectricity: How endogenous
    voltage potentials control cell behavior and instruct pat-
    tern regulation in vivo. Mol Biol Cell 2014;25:3835–3850.
  2. Shi R, Borgens RB. Three-dimensional gradients of voltage during development of the nervous system as in- visible coordinates for the establishment of embryonic
    pattern. Dev Dyn 1995;202:101–114.
  3. Borgens RB, Shi R. Uncoupling histogenesis from mor-
    phogenesis in the vertebrate embryo by collapse of the
    transneural tube potential. Dev Dyn 1995;203:456–467.
  4. Jenkins LS, Duerstock BS, Borgens RB. Reduction of the current of injury leaving the amputation inhibits limb regen- eration in the red spotted newt. Dev Biol 1996;178:251–262.
  5. Jaffe L. The role of ionic currents in establishing devel- opmental pattern. Philos Trans R Soc Lond Ser 1981;295:
    553–566.
  6. Burr HS, Northrop F. The electrodynamic theory of life. Q
    Rev Biol 1935;10:322–333.
  7. Burr HS. The meaning of bioelectric potentials. Yale J
    Biol Med 1944;16:353–360.
  8. Lund E. Bioelectric Fields and Growth. Austin, TX:
    University of Texas Press, 1947.
  9. Marsh G, Beams HW. Electrical control of growth polarity
    in regenerating Dugesia tigrina. Fed Proc 1947;6:163–164.
  10. Marsh G, Beams HW. Electrical control of axial polarity
    in a regenerating annelid. Anat Rec 1949;105:513–514.
  11. Marsh G, Beams HW. Electrical control of morphogenesis in regenerating Dugesia tigrina. I. Relation of axial polarity
    to field strength. J Cell Comp Physiol 1952;39:191–213.
  12. Johnstone BM. Micro-electrode penetration of ascites tu-
    mour cells. Nature 1959;183:411.
  13. Aloysio Luigi Galvani (1737–1798) discoverer of animal
    electricity. JAMA 1967;201:626–627.
39. Murata Y, Iwasaki H, Sasaki M, et al. Phosphoinositide phosphatase activity coupled to an intrinsic voltage sen- sor. Nature 2005;435:1239–1243.
40. Zhao M. Electrical fields in wound healing—An overrid- ing signal that directs cell migration. Semin Cell Dev Biol 2009;20:674–682.
41. Zhao M, Song B, Pu J, et al. Electrical signals control wound healing through phosphatidylinositol-3-OH kinase- gamma and PTEN. Nature 2006;442:457–460.
42. Levin M. Endogenous bioelectrical networks store non- genetic patterning information during development and regeneration. J Physiol 2014;592:2295–2305.
43. Levin M. Large-scale biophysics: Ion flows and regener- ation. Trends Cell Biol 2007;17:261–270.
44. Levin M. Morphogenetic fields in embryogenesis, regen- eration, and cancer: Non-local control of complex pat- terning. Biosystems 2012;109:243–261.
45. Mauro A. Satellite cell of skeletal muscle fiber. J Biophys Biochem Cytol 1961;9:493–495.
46. Dhawan J, Rando TA. Stem cells in postnatal myogenesis: Molecular mechanisms of satellite cell quiescence, activa- tion and replenishment. Trends Cell Biol 2005;15:666–673.
47. Snow MH. An autoradiographic study of satellite cell dif- ferentiation into regenerating myotubes following trans- plantation of muscles in young rats. Cell Tissue Res 1978; 186:535–540.
48. Conboy IM, Conboy CJ, Wagers AJ, et al. Rejuvination of aged proginator cells by exposure to young systemic en- vironment. Nature 2005;433:760–764.
49. Brack AS, Conboy MJ, Roy S, et al. Increased Wnt sig- naling during aging alters muscle stem cell fate and in- creases fibrosis. Science 2007;317:807–810.
50. Chakkalakal JV, Jones KM, Basson MA, et al. The aged niche disrupts muscle stem cell quiescence. Nature 2012; 490:355–360.
Downloaded by 24.11.114.253 from www.liebertpub.com at 02/10/19. For personal use only.
36
FENNELLY AND SOKER
  1. Brack AS, Mun ̃ oz-Ca ́ noves P. The ins and outs of muscle stem cell aging. Skelet Muscle 2016;6:1.
  2. Goodell MA, Rando TA. Stem cells and healthy aging. Science 2015;350:1199–1204.
  3. Jones DL, Wagers AJ. No place like home: Anatomy and function of the stem cell niche. Nat Rev Mol Cell Biol 2008;9:11–21.
  4. Oh J, Lee YD, Wagers AJ. Stem cell aging: Mechanisms, regulators and therapeutic opportunities. Nat Med 2014; 20:870–880.
  5. Wagers AJ. The stem cell niche in regenerative medicine. Cell Stem Cell 2012;10:362–369.
  6. Gopinath SD, Rando TA. Stem cell review series: Aging of the skeletal muscle stem cell niche. Aging Cell 2008;7: 590–598.
  7. Sacco A, Doyonnas R, Kraft P, et al. Self-renewal and expansion of single transplanted muscle stem cells. Nature 2008;456:502–506.
  8. Cosgrove BD, Sacco A, Gilbert PM, et al. A home away from home: Challenges and opportunities in engineering in vitro muscle satellite cell niches. Differentiation 2009; 78:185–194.
  9. Gilbert PM, Havenstrite KL, Magnusson KE, et al. Sub- strate elasticity regulates skeletal muscle stem cell self- renewal in culture. Science 2010;329:1078–1081.
  10. Charge ́S,RudnickiMA.Cellularandmolecularregula- tion of muscle regeneration. Physiol Rev 2004;84:209– 238.
  11. Wagers AJ, Conboy IM. Cellular and molecular signatures of muscle regeneration: Current concepts and controver- sies in adult myogenesis. Cell 2005;122:659–667.
  12. Cerletti M, Shadrach JL, Jurga S, et al. Regulation and function of skeletal muscle stem cells. Cold Spring Harb Symp Quant Biol 2008;73:317–322.
  13. Tedesco FS, Dellavalle A, Diaz-Manera J, et al. Repairing skeletal muscle: Regenerative potential of skeletal muscle stem cells. J Clin Invest 2010;120:11–19.
  14. Collins CA, Olsen I, Zammit PS, et al. Stem cell function, self-renewal, and behavioral heterogeneity of cells from the adult muscle satellite cell niche. Cell 2005;122:289–301.
  15. Konig S, Beguet A, Bader CR, et al. The calcineurin pathway links hyperpolarization (Kir2.1)-induced Ca2+ signals to human myoblast differentiation and fusion. Development 2006;133:3107–3114.
  16. Binggeli R, Weinstein R. Membrane potentials and so- dium channels: hypotheses for growth regulation and cancer formation based on changes in sodium channels and gap junctions. J Theor Biol 1986;123:377–401.
  17. Levin M. Molecular bioelectricity in developmental bi- ology: New tools and recent discoveries: Control of cell behavior and pattern formation by transmembrane poten- tial gradients. Bioessays 2012;34:205–217.
  18. Cone CD Jr. Electroosmotic interactions accompanying mitosis initation in sarcoma cells in vitro. Trans N Y Acad Sci 1969;31:404–427.
  19. Cone CD Jr. Variation of the transmembrane potential level as a basic mechanism of mitosis control. Oncology 1970;6:438–470.
  20. Cone CD Jr., Tongier MJ. Control of somatic cell mitosis by simulated changes in the transmembrane potential le- vel. Oncology 1971;2:168–182.
  21. Cone CD Jr. Unified theory on the basic mechanism of normal mitotic control and oncogenesis. J Theor Biol 1971;30:151–181.
72. Cone CD Jr. The role of the surface electrical trans- membrane potential in normal and malignant mitogenesis. Ann N Y Acad Sci 1974;238:420–435.
73. Wang E, Yin Y, Zhao M, et al. Physiological electric fields control the G1/S phase cell cycle checkpoint to inhibit endothelial cell proliferation. FASEB J 2003;17:458–460.
74. Kong SK, Suen YK, Choy YM, et al. Membrane depo- larization was required to induce DNA synthesis in murine macrophage cell line PU5-1.8. Immunopharmacol Im- munotoxicol 1991;13:329–339.
75. Macfarlane SN, Sontheimer H. Changes in ion channel expression accompany cell cycle progression of spinal cord astrocytes. Glia 2000;30:39–48.
76. Woodfork KA, Wonderlin WF, Peterson VA, et al. In- hibition of ATP-sensitive potassium channels causes re- versible cell-cycle arrest of human breast cancer cells in tissue culture. J Cell Physiol 1995;162:163–171.
77. Pardo LA, Bru ̈ggemann A, Camacho J, et al. Cell cycle– related changes in the conducting properties of r-eag K1 channels. J Cell Biol 1998;143:767–775.
78. Chen L, Wang L, Zhu L, et al. Cell cycle-dependent ex- pression of volume-activated chloride currents in naso- pharyngeal carcinoma cells. Am J Physiol Cell Physiol 2002;283:c1313–c1323.
79. Valenzuela SM, Mazzanti M, Tonini R, et al. The nuclear chloride ion channel NCC27 is involved in regulation of the cell cycle. J Physiol 2000;529 Pt 3:541–552.
80. Zheng YJ, Furukawa T, Ogura T, et al. M phase-specific expression and phosphorylation-dependent ubiquitination of the ClC-2 channel. J Biol Chem 2002;277:32268– 32273.
81. Grissmer S, Nguyen AN, Cahala MD. Calcium-activated potassium channels in resting and activated human T lymphocytes. J Gen Physiol 1993;102:601–630.
82. Lovisolo D, Bonelli G, Baccino FM, et al. Two currents activated by epidermal growth factor in EGFR-T17 fi- broblasts. Biochem Biophys 1992;1104:73–82.
83. Magni M, Meldolesi J, Pandiella A. Ionic events induced by epidermal growth factor: Evidence that hyperpolar- ization and stimulated cation influx play a role in the stimulation of cell growth. J Biol Chem 1991;266:6329– 6335.
84. Boonstra J, Mummery CL, Tertoolen L, et al. Cation transport and growth regulation in neuroblastoma cells. Modulations of K+ transport and electrical membrane properties during the cell cycle. J Cell Physiol 1981;107: 75–83.
85. Mummery C, Boonstra J, Saag PT, et al. Modulations of Na+ transport during the cell cycle of neuroblastoma cells. J Cell Physiol 1982;112:27–34.
86. Partiseti M, Korn H, Choquet D. Pattern of potassium channel expression in proliferating B lymphocytes de- pends upon the mode of activation. J Immunol 1993;151: 2462–2470.
87. Ouadid-Ahidouch H, Roudbaraki M, Delcourt P, et al. Functional and molecular identification of intermediate- conductance Ca2+-activated K+ channels in breast cancer cells: association with cell cycle progression. Am J Phy- siol Cell Physiol 2004;287:c125–c134.
88. Ouadid-Ahidouch H, Le Bourhis X, Roudbaraki M, et al. Changes in the K+ current-density of MCF-7 cells during progression through the cell cycle: Possible involvement of a h-ether.a-gogo K+ channel. Receptors Channels 2007; 5:345–356.
Downloaded by 24.11.114.253 from www.liebertpub.com at 02/10/19. For personal use only.
MPC BIOELECTRICITY 37
  1. Wilson GF, Chiu SY. Mitogenic factors regulate ion channels in Schwann cells cultured from newborn rat sciatic nerve. J Physiol 1993;470:501–520.
  2. Decoursey TE, Chandy KG, Gupta S, et al. Mitogen in- duction of ion channels in murine T lymphocytes. J Gen Physiol 1987;89:405–420.
  3. Deutsch C, Krause D. Voltage-gated potassium conduc- tance in human T lymphocytes stimulated with phorbol ester. J Physiol 1986;371:405–423.
  4. Enomoto K-i, Cossu MF, Maeno T, et al. Involvement of the Ca2+-dependent K+ channel activity in the hyperpo- larizing response induced by epidermal growth factor in mammary epithelial cells. FEBS Lett 1986;203:181–184.
  5. Hamann M, Widmer H, Baroffio A, et al. Sodium and potassium currents in freshly isolated and in proliferating human muscle satellite cells. J Physiol 1994;475:305–317.
  6. Kubo Y. Comparison of initial stages of muscle differ- entiation in rat and mouse myoblastic and mouse meso- dermal stem cell lines. J Physiol 1991;442:743–759.
  7. Liu JH, Bijlenga P, Fischer-Lougheed J, et al. Role of an inward rectifier K+ current and of hyperpolarization in human myoblast fusion. J Physiol 1998;510:467–476.
  8. Bijlenga P, Occhiodoro T, Liu JH, et al. An ether-a`-go-go K+ current, Ih-eag, contributes to the hyperpolarization of human fusion-competent myoblasts. J Physiol 1998;512: 317–322.
  9. Fennelly C, Wang Z, Criswell T, et al. Sustained depo- larization of the resting membrane potential regulates muscle progenitor cell growth and maintains stem cell properties in vitro. Stem Cell Rev 2016;12:634–644.
  10. Yasuda T, Bartlett PF, Adams DJ. K(ir) and K(v) channels regulate electrical properties and proliferation of adult neural precursor cells. Mol Cell Neurosci 2008;37:284–297.
  11. Orr CW, Yoshikawa-Fukada M, Ebert M. Potassium: Effect on DNA synthesis and multiplication of baby- hamster kidney cells. Proc Natl Acad Sci U S A 1972;69: 243–247.
  12. Freedman BD, Price MA, Deutsch CJ. Evidence for voltage modulation of IL-2 production in mitogen- stimulated human peripheral blood lymphocytes. J Im- munol 1992;149:3784–3794.
  13. Canady KS, Ali-Osman F, Rubel EW. Extracellular po- tassium influences DNA and protein syntheses and glial fibrillary acidic protein expression in cultured glial cells. Glia 1990;3:368–374.
  14. Ghiani CA, Yuan X, Eisen AM, et al. Voltage-activated K1 channels and membrane depolarization regulate ac- cumulation of the cyclin-dependent kinase inhibitors p27Kip1 and p21CIP1 in glial progenitor cells. J Neurosci 1999;19:5380–5392.
  15. Cone CD Jr., Cone CM. Induction of mitosis in mature neurons in central nervous system by sustained depolar- ization. Science 1976;192:155–158.
  16. Stillwell EF, Cone CM, Cone CD. Stimulation of DNA synthesis in CNS neurons by sustained depolarization. Nature 1973;246:110–111.
  17. Lan JY, Williams C, Levin M, et al. Depolarization of cellular resting membrane potential promotes neonatal cardiomyocyte proliferation in vitro. Cell Mol Bioeng 2014;7:432–445.
  18. Arcangeli A, Bianchi L, Becchetti A, et al. A novel inward-rectifying K+ current with a cell-cycle dependence governs the resting potential of mammalian neuroblas- toma cells. J Physiol 1995;489:455–471.
107. Higashimori H, Sontheimer H. Role of Kir4.1 channels in growth control of glia. Glia 2007;16:1668–1679.
108. O’Connell KM, Tamkun MM. Targeting of voltage-gated potassium channel isoforms to distinct cell surface mi- crodomains. J Cell Sci 2005;118:2155–2166.
109. O’Connell KM, Rolig AS, Whitesell JD, et al. Kv2.1 potassium channels are retained within dynamic cell sur- face microdomains that are defined by a perimeter fence. J Neurosci 2006;26:9609–9618.
110. Cai J, Cheng A, Luo Y, et al. Membrane properties of rat embryonic multipotent neural stem cells. J Neurochem 2004;88:212–226.
111. Yu K, Ruan DY, Ge SY. Three electrophysiological phenotypes of cultured human umbilical vein endothelial cells. Gen Physiol Biophys 2002;21:315–326.
112. Heubach JF, Graf EM, Leutheuser J, et al. Electro- physiological properties of human mesenchymal stem cells. J Physiol 2004;554:659–672.
113. Li GR, Sun H, Deng X, et al. Characterization of ionic currents in human mesenchymal stem cells from bone marrow. Stem Cells 2005;23:371–382.
114. Bai X, Ma J, Pan Z, et al. Electrophysiological properties of human adipose tissue-derived stem cells. Am J Physiol Cell Physiol 2007;293:C1539–C1550.
115. Biagiotti T, D’Amico M, Marzi I, et al. Cell renewing in neuroblastoma: Electrophysiological and immunocyto- chemical characterization of stem cells and derivatives. Stem Cells 2006;24:443–453.
116. Gersdorff Korsgaard MP, Christophersen P, Ahring PK, et al. Identification of a novel voltage-gated Na+ channel rNa(v)1.5a in the rat hippocampal progenitor stem cell line HiB5. Pflugers Arch 2001;443:18–30.
117. Sun W, Buzanska L, Domanska-Janik K, et al. Voltage- sensitive and ligand-gated channels in differentiating neural stem-like cells derived from the nonhematopoietic fraction of human umbilical cord blood. Stem Cells 2005;23:931–945.
118. Cho T, Bae JH, Choi HB, et al. Human neural stem cells: Electrophysiological properties of voltage-gated ion channels. Neuroreport 2002;11:1447–1452.
119. Chafai M, Louiset E, Basille M, et al. PACAP and VIP promote initiation of electrophysiological activity in dif- ferentiating embryonic stem cells. Ann N Y Acad Sci 2006;1070:185–189.
120. Balana B, Nicoletti C, Zahanich I, et al. 5-Azacytidine induces changes in electrophysiological properties of hu- man mesenchymal stem cells. Cell Res 2006;16:949–960.
121. Ravens U. Electrophysiological properties of stem cells. Herz 2006;2:123–126.
122. Wenisch S, Trinkaus K, Hild A, et al. Immunochemical, ultrastructural and electrophysiological investigations of bone-derived stem cells in the course of neuronal differ- entiation. Bone 2006;38:911–921.
123. Park KS, Jung KH, Kim SH, et al. Functional expression of ion channels in mesenchymal stem cells derived from umbilical cord vein. Stem Cells 2007;25:2044–2052.
124. Sundelacruz S, Levin M, Kaplan DL. Membrane potential controls adipogenic and osteogenic differentiation of mesenchymal stem cells. PLoS One 2008;3:e3737.
125. Sundelacruz S, Levin M, Kaplan DL. Depolarization alters phenotype, maintains plasticity of predifferentiated mesen- chymal stem cells. Tissue Eng Part A 2013;19:1889–1908.
126. Fischbach GD, Nameroff M, Nelson PG. Electrical properties of chick skeletal muscle fibers developing in cell culture. J Cell Physiol 1971;78:289–299.
Downloaded by 24.11.114.253 from www.liebertpub.com at 02/10/19. For personal use only.
38
FENNELLY AND SOKER
  1. Ritchie AK, Fambrough DM. Electrophysiological prop- erties of the membrane and acetylcholine receptor in de- veloping rat and chick myotubes. J Gen Physiol 1975;66: 327–355.
  2. Spector I, Prives JM. Development of electrophysiological and biochemical membrane properties during differentia- tion of embryonic skeletal muscle in culture. Proc Natl Acad Sci U S A 1977;74:5166–5170.
  3. Fischer-Lougheed J, Liu JH, Espinos E, et al. Human myoblast fusion requires expression of functional inward rectifier Kir2.1 channels. J Cell Biol 2001;153:677–685.
  4. Hille B. Ionic channels in excitable membranes. Current problems and biophysical approaches. Biophys J 1978;22: 283–294.
  5. Shirihai O, Attali B, Degan D, et al. Expression of two inward rectifier potassium channels is essential for dif- ferentiation of primitive human hematopoietic progenitor cells. J Cell Physiol 1998;177:197–205.
  6. Gronemeier M, Condie A, Prosser J, et al. Nonsense and missense mutations in the muscular chloride channel gene CIc-1 of myotonic mice. J Biol Chem 1994;269:5963– 5967.
  7. Bardouille C, Vullhorst D, Jockusch H. Expression of chloride channel 1 mRNA in cultured myogenic cells a marker of myotube maturation. FEBS Lett 1996;396:177– 180.
  8. Bernheim L, Bader C. Human myoblast differentiation: Ca2+ channels are activated by K+ channels. News Phy- siol Sci 2002;17:22–26.
  9. Liu JH. Acceleration of human myoblast fusion by de- polarization: Graded Ca2+ signals involved. Development 2003;130:3437–3446.
  10. Konig S, Hinard V, Arnaudeau S, et al. Membrane hy- perpolarization triggers myogenin and myocyte enhancer factor-2 expression during human myoblast differentia- tion. J Biol Chem 2004;279:28187–28196.
  11. Skuk D, Goulet M, Chapdelaine P, et al. Dystrophin ex- pression in muscles of duchenne muscular dystrophy pa- tients after high-density injections of normal myogenic cells. J Neuropathol Exp Neurol 2006;65:371–386.
  12. Tremblay JP, Skuk D. Another new ‘‘super muscle stem cell’’ leaves unaddressed the real problems of cell therapy for duchenne muscular dystrophy. Mol Ther 2008;16: 1907–1909.
  13. Darbellay B, Arnaudeau S, Konig S, et al. STIM1- and Orai1-dependent store-operated calcium entry regulates human myoblast differentiation. J Biol Chem 2009;284: 5370–5380.
144. Fakler B, Bra ̈ndle U, Glowatzki E, et al. Kir2.1 inward rectifier K+ channels are regulated independently by pro- tein kinases and ATP hydrolysis. Nature 1994;13:1413– 1420.
145. Jones SV. Role of the small GTPase Rho in modulation of the inwardly rectifying potassium channel Kir2.1. Mol Pharmacol 2003;64:987–993.
146. Giovannardi S, Forlani G, Balestrini M, et al. Modulation of the inward rectifier potassium channel IRK1 by the Ras signaling pathway. J Biol Chem 2002;277:12158–12163.
147. Sampson LJ, Leyland ML, Dart C. Direct interaction be- tween the actin-binding protein filamin-A and the in- wardly rectifying potassium channel, Kir2.1. J Biol Chem 2003;278:41988–41997.
148. Leonoudakis D, Conti LR, Radeke CM, et al. A multi- protein trafficking complex composed of SAP97, CASK, Veli, and Mint1 is associated with inward rectifier Kir2 potassium channels. J Biol Chem 2004;279:19051–19063.
149. Leyland ML, Dart C. An alternatively spliced isoform of PSD-93/chapsyn 110 binds to the inwardly rectifying potassium channel, Kir2.1. J Biol Chem 2004;279:43427– 43436.
150. Roha ́cs T, Lopes CM, Jin T, et al. Specificity of activation by phosphoinositides determines lipid regulation of Kir channels. Proc Natl Acad Sci U S A 2003;100:745–750.
151. Hansen SB, Tao X, MacKinnon R. Structural basis of PIP2 activation of the classical inward rectifier K+ chan- nel Kir2.2. Nature 2011;477:495–498.
152. Li J, Lu ̈ S, Liu Y, et al. Identification of the conforma- tional transition pathway in PIP2 opening Kir channels. Sci Rep 2015;5:11289.
153. Soom M, Scho ̈nherr R, Kubo Y, et al. Multiple PIP2 binding sites in Kir2.1 inwardly rectifying potassium channels. FEBS Lett 2001;490:49–53.
154. Leem YE, Jeong HJ, Kim HJ, et al. Cdo regulates surface expression of Kir2.1 K+ channel in myoblast differentia- tion. PLoS One 2016;11:e0158707.
155. Dahlmann A, Li M, Gao Z, et al. Regulation of Kir channels by intracellular pH and extracellular K(+): Me- chanisms of coupling. J Gen Physiol 2004;123:441–454.
156. Firth TA, Jones SV. GTP-binding protein Gq mediates muscarinic-receptor-induced inhibition of the inwardly rectifying potassium channel IRK1 (Kir 2.1). Neuro- pharmacology 2001;40:358–365.
157. Hoger JH, Llyin VI, Forsyth S, et al. Shear stress regulates the endothelial Kir2.1 ion channel. Proc Natl Acad Sci U S A 2002;99:7780–7785.
158. Ruppersberg JP, Fakler B. Complexity of the regulation of Kir2.1 K+ channels. Neuropharmacology 1996;35:887–
140. Antigny F, Koenig S, Bernheim L, et al. During post-natal
human myogenesis, normal myotube size requires 893.
TRPC1- and TRPC4-mediated Ca(2)(+) entry. J Cell Sci
2013;126:2525–2533.
  1. Hinard V, Belin D, Konig S, et al. Initiation of human
    myoblast differentiation via dephosphorylation of Kir2.1 K+ channels at tyrosine 242. Development 2008;135:859– 867.
  2. Wischmeyer E, Do ̈ring F, Karschin A. Acute suppression of inwardly rectifying Kir2.1 channels by direct tyrosine kinase phosphorylation. J Biol Chem 1998;273:34063– 34068.
  3. Wischmeyer E, Karschin A. Receptor stimulation causes slow inhibition of IRK1 inwardly rectifying K+ channels by direct protein kinase A-mediated phosphorylation. Proc Natl Acad Sci U S A 1996;93:5819–5823.
159. Ruppersberg JP. Intracellular regulation of inward rectifier K+ channels. Pflugers Arch 2000;441:1–11.
160. Zhao M, Forrester JV, McCaig CD. A small, physiological electric field orients cell division. Proc Natl Acad Sci U S A 1999;96:4942–4946.
161. Song B, Zhao M, Forrester JV, et al. Electrical cues reg- ulate the orientation and frequency of cell division and the rate of wound healing in vivo. Proc Natl Acad Sci U S A 2002;99:13577–13582.
162. Przewoz ́ niak M, Czaplicka I, Czerwin ́ ska AM, et al. Ad- hesion proteins—An impact on skeletal myoblast differ- entiation. PLoS One 2013;8:e61760.
163. Perumal Srinivasan S, Neef K, Treskes P, et al. Enhanced gap junction expression in myoblast-containing en-
Downloaded by 24.11.114.253 from www.liebertpub.com at 02/10/19. For personal use only.
MPC BIOELECTRICITY 39
gineered tissue. Biochem Biophys Res Commun 2012;8:
462–468.
  1. Me`ge RM, Goudou D, Giaume C, et al. Is intercellular
    communication via gap junctions required for myoblast
    fusion? Cell Adhes Commun 1994;2:329–343.
  2. Mege RM, Goudou D, Diaz C, et al. N-cadherin and N- CAM in myoblast fusion: Compared localisation and ef- fect of blockade by peptides and antibodies. J Cell Sci
    1992;103:897–906.
  3. Araya R, Eckardt D, Riquelme MA, et al. Presence and
    importance of connexin43 during myogenesis. Cell
    Commun Adhes 2003;10:451–456.
  4. Araya R, Eckardt D, Maxeiner S, et al. Expression of
    connexins during differentiation and regeneration of skeletal muscle: Functional relevance of connexin43. J Cell Sci 2005;118:27–37.
  5. Constantin B, Cronier L, Raymond G. Transient in- volvement of gap junctional communication before fusion of newborn rat myoblasts. C R Acad Sci III 1997;320: 35–40.
  6. Constantin B, Cronier L. Involvement of gap junctional communication in myogenesis. Int Rev Cytol 2000;196: 1–65.
  7. Morabito C, Steimberg N, Rovetta F, et al. Extremely low-frequency electromagnetic fields affect myogenic processes in C2C12 myoblasts: Role of Gap-junction- mediated intercellular communication. Biomed Res Int 2017;2017:2460215.
  8. Proulx A, Merrifield PA, Naus CC. Blocking gap junc- tional intercellular communication in myoblasts inhibits myogenin and MRF4 expression. Dev Genet 1997;20: 133–144.
  9. Beane WS, Morokuma J, Adams DS, et al. A chemical genetics approach reveals H,K-ATPase-mediated mem- brane voltage is required for planarian head regeneration. Chem Biol 2011;18:77–89.
  10. Tseng A, Levin M. Cracking the bioelectric code: Probing endogenous ionic controls of pattern formation. Commun Integr Biol 2013;6:e22595.
  11. Tseng AS, Beane WS, Lemire JM, et al. Induction of vertebrate regeneration by a transient sodium current. J Neurosci 2010;30:13192–13200.
  12. Day ML, Pickering SJ, Johnson MH, et al. Cell-cycle control of a large-conductance K+ channel in mouse early embryos. Nature 1993;365:560–562.
  13. Sachs HG, Stambrook PJ, Ebert JD. Changes in membrane potential during the cell cycle. Exp Cell Res 1974;83:362– 366.
  14. Block ML, Moody WJ. A voltage-dependent chloride current linked to the cell cycle in ascidian embryos. Sci- ence 1990;247:1090–1092.
  15. Habela CW, Olsen ML, Sontheimer H. ClC3 is a critical regulator of the cell cycle in normal and malignant glial cells. J Neurosci 2008;28:9205–9217.
179. Wang Z, Cheung D, Zhou Y, et al. An in vitro culture system that supports robust expansion and maintenance of in vivo engraftment capabilities for myogenic progenitor cells from adult mice. Biores Open Access 2014;3:79–87.
180. Charville GW, Cheung TH, Yoo B, et al. Ex vivo ex- pansion and in vivo self-renewal of human muscle stem cells. Stem Cell Reports 2015;5:621–632.
181. Ostrovidov S, Hosseini V, Ahadian S, et al. Skeletal muscle tissue engineering: Methods to form skeletal myotubes and their applications. Tissue Eng Part B Rev 2104;20:403–436.
182. Fu X, Xiao J, Wei Y, et al. Combination of inflammation- related cytokines promotes long-term muscle stem cell expansion. Cell Res 2015;25:655–673.
183. Quarta M, Brett JO, DiMarco R, et al. An artificial niche preserves the quiescence of muscle stem cells and en- hances their therapeutic efficacy. Nat Biotechnol 2016;34: 752–759.
184. Cerletti M, Jurga S, Witczak CA, et al. Highly efficient, functional engraftment of skeletal muscle stem cells in dystrophic muscles. Cell 2008;134:37–47.
185. Montarras D, Morgan J, Collins C, et al. Direct isolation of satellite cells for skeletal muscle regeneration. Science 2005;309:2064–2067.
186. Famm K, Litt B, Tracey KJ, et al. Drug discovery: A jump-start for electroceuticals. Nature 2013;496:159–161. 187. Sinha G. Charged by GSK investment, battery of elec-
troceuticals advance. Nat Med 2013;19:654.
188. Wang YX, Dumont NA, Rudnicki MA. Muscle stem cells
at a glance. J Cell Sci 2014;127:4543–4548.
189. Mann CJ, Perdiguero E, Kharraz Y, et al. Aberrant repair and fibrosis development in skeletal muscle. Skelet Mus-
cle 2011;1:21.
190. Kuang S, Charge SB, Seale P, et al. Distinct roles for Pax7
and Pax3 in adult regenerative myogenesis. J Cell Biol
2006;172:103–113.
191. Oustanina S, Hause G, Braun T. Pax7 directs postnatal
renewal and propagation of myogenic satellite cells but
not their specification. EMBO J 2004;23:3430–3439. 192. Relaix F, Rocancourt D, Mansouri A, et al. A Pax3/Pax7- dependent population of skeletal muscle progenitor cells.
Nature 2005;435:948–953.
193. Seale P, Sabourin LA, Girgis-Gabardo A, et al. Pax7 is
required for the specification of myogenic satellite cells. Cell 2000;102:777–786.
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