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Pre-treatment of mesenchymal stem cells with a combination of growth factors enhances gap junction formation, cytoprotective effect on cardiomyocytes, and therapeutic efficacy for myocardial infarction

Cited 235 time in Web of Science Cited 247 time in Scopus
Authors
Hahn, Joo-Yong; Cho, Hyun-Ju; Kang, Hyun-Jae; Kim, Tack-Seung; Kim, Mi-Hyung; Chung, Jung-Hwa; Bae, Jang-Whan; Oh, Byung-Hee; Park, Young-Bae; Kim, Hyo-Soo
Issue Date
2008-03-01
Publisher
Elsevier
Citation
J Am Coll Cardiol. 2008;51(9):933-943
Keywords
AnimalsBone Morphogenetic Protein 2Bone Morphogenetic Proteins/*pharmacologyCell Differentiation/drug effectsDisease Models, AnimalFibroblast Growth Factor 2/*pharmacologyGap Junctions/*drug effects/metabolismGene ExpressionInsulin-Like Growth Factor I/*pharmacologyMaleMesenchymal Stem Cell TransplantationMesenchymal Stem Cells/*drug effectsMyocardial Infarction/*therapyMyocytes, Cardiac/*drug effects/metabolismRatsRats, Inbred F344Transforming Growth Factor beta/*pharmacology
Abstract
OBJECTIVES: The goal of this study was to investigate the effect of pre-treatment of mesenchymal stem cells (MSCs) with growth factors (GFs) on cardiomyogenic differentiation, cytoprotective action on cardiomyocytes (CMCs), and their therapeutic efficacy in myocardial infarction. BACKGROUND: Mechanisms of myocardial repair with MSC transplantation have not been fully elucidated, and therapeutic efficacy needs to be enhanced. METHODS: The MSCs obtained from the bone marrow of Fisher344 rats were treated with fibroblast growth factor-2, insulin-like growth factor-1, and bone morphogenetic protein-2. The expression of cardiac specific markers and the cytoprotective effect of MSCs with its mechanism were evaluated. Efficacy of MSCs transplantation was studied in rat myocardial infarction model. RESULTS: Treatment of MSCs with cocktails of GFs enhanced expression of cardiac transcription factors and survival. Induction of cardiac specific markers by coculture with CMCs and gap junctional communication with CMCs was more active in GF-treated MSCs than untreated MSCs. The GF-treated MSCs reduced apoptosis of neighboring CMCs in a hypoxic condition and enhanced the phosphorylated Akt and phosphorylated c-AMP response element binding protein expression of CMCs, which was markedly reduced by gap junction blockade. In a rat myocardial infarction model, transplantation of GF-treated MSCs resulted in smaller infarct size and better cardiac function than transplantation of untreated MSCs. Additionally, GF treatment enhanced gap junction formation of transplanted MSCs, which did not aggravate arrhythmia. CONCLUSIONS: Pre-treatment of MSCs with GFs enhanced cytoprotective effects on neighboring CMCs through gap junction and improved the therapeutic efficacy of MSC transplantation for myocardial repair. "Priming of MSCs with GFs" before transplantation might improve the therapeutic efficacy of cell therapy.
ISSN
1558-3597 (Electronic)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18308163

http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6T18-4RXN2M5-B-8&_cdi=4884&_user=168665&_orig=search&_coverDate=03%2F04%2F2008&_sk=999489990&view=c&wchp=dGLbVlW-zSkzk&md5=133bf0cd261f4fdb667bdb807e1e7b62&ie=/sdarticle.pdf

https://hdl.handle.net/10371/68189
DOI
https://doi.org/10.1016/j.jacc.2007.11.040
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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