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Phorbol myristate acetate differentiates human adipose-derived mesenchymal stem cells into functional cardiogenic cells

Authors
 Woochul Chang  ;  Soyeon Lim  ;  Byeong-Wook Song  ;  Chang Youn Lee  ;  Moon-Seo Park  ;  Young-An Chung  ;  Cheesoon Yoon  ;  Se-Yeon Lee  ;  Onju Ham  ;  Jun-Hee Park  ;  Eunhyun Choi  ;  Lee-So Maeng  ;  Ki-Chul Hwang 
Citation
 Biochemical and Biophysical Research Communications, Vol.424(1) : 740-746, 2012 
Journal Title
 Biochemical and Biophysical Research Communications 
ISSN
 0006-291X 
Issue Date
2012
MeSH
Adipose Tissue/cytology* ; Animals ; Cell Culture Techniques ; Cell Differentiation/drug effects* ; Cells, Cultured ; Humans ; Male ; Mesenchymal Stromal Cells/cytology ; Mesenchymal Stromal Cells/drug effects* ; Myocardial Ischemia/therapy ; Myocytes, Cardiac/cytology* ; Myocytes, Cardiac/transplantation ; Rats ; Rats, Sprague-Dawley ; Regeneration/genetics ; Tetradecanoylphorbol Acetate/pharmacology*
Keywords
Adipose-derived mesenchymal stem cells ; Cardiac regeneration ; Cardiogenic differentiation ; Protein kinase C
Abstract
To achieve effective regeneration of injured myocardium, it is important to find physiological way of improving the cardiogenic differentiation of stem cells. Previous studies demonstrated that cardiomyocytes from bone marrow-derived mesenchymal stem cells (BMSCs) activated with phorbolmyristate acetate (PMA), a protein kinase C (PKC) activator, restore electromechanical function in infarcted rat hearts. In this study, we investigated the effect of PMA on cardiogenic differentiation of adipose-derived MSCs (ASCs) for clinical applications. To confirm the effect of PMA, ASCs treated with 1μM PMA were grown for nine days. The expression of cardiac-specific markers (cardiac troponin T, myosin light chain, myosin heavy chain) in PMA-treated MSCs was demonstrated by immunocytochemistry. Alhough few α(1A) receptors exist in ASCs, α(1)-adrenergic receptor subtypes were preferentially expressed in PMA-treated ASCs. Moreover, expression of the β-adrenergic and muscarinic receptors increased in PMA-treated ASCs compared to normal cells. The mRNA levels of Ca(2+)-related factors (SERCA 2a; sarcoplasmic reticulum Ca(2+)-ATPase, LTCC; L-type Ca(2+) channel) in treated ASCs were similar to the levels in cardiomyocytes. Following the transplantation of chemically activated cardiogenic ASCs into infarcted myocardium, histological analysis showed that infarct size, interstitial fibrosis, and apoptotic index were markedly decreased and cardiac function was restored. In conclusion, PMA might induce the cardiogenic differentiation of human ASCs as well as BMSCs. This result suggests successful use of human ASCs in cardiac regeneration therapy.
Full Text
http://www.sciencedirect.com/science/article/pii/S0006291X12013058
DOI
22809507
Appears in Collections:
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
5. Research Institutes (연구소) > Yonsei Integrative Research Institute for Cerebral & Cardiovascular Disease (뇌심혈관질환융합연구사업단) > 1. Journal Papers
5. Research Institutes (연구소) > Yonsei Cardiovascular Research Institute (심혈관연구소) > 1. Journal Papers
Yonsei Authors
Park, Jun-Hee(박준희)
Song, Byeong Wook(송병욱)
Lee, Se Yeon(이세연)
Lee, Chang Yeon(이창연)
Lim, So Yeon(임소연)
Choi, Eun Hyun(최은현)
Ham, On Ju(함온주)
Hwang, Ki Chul(황기철)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/89709
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