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Cardiomyocytes from phorbol myristate acetate-activated mesenchymal stem cells restore electromechanical function in infarcted rat hearts

Authors
 Heesang Song  ;  Hye Jin Hwang  ;  Woochul Chang  ;  Byeong-Wook Song  ;  Min-Ji Cha  ;  Il-Kwon Kim  ;  Soyeon Lim  ;  Eun Ju Choi  ;  Onju Ham  ;  Chang Youn Lee  ;  Jun-Hee Park  ;  Se-Yeon Lee  ;  Eunmi Choi  ;  Chungkeun Lee  ;  Myoungho Lee  ;  Moon-Hyoung Lee  ;  Sung-Hou Kim  ;  Yangsoo Jang  ;  Ki-Chul Hwang 
Citation
 Proceedings of the National Academy of Sciences of the United States of America, Vol.108(1) : 296-301, 2011 
Journal Title
 Proceedings of the National Academy of Sciences of the United States of America 
ISSN
 0027-8424 
Issue Date
2011
Abstract
Despite the safety and feasibility of mesenchymal stem cell (MSC) therapy, an optimal cell type has not yet emerged in terms of electromechanical integration in infarcted myocardium. We found that poor to moderate survival benefits of MSC-implanted rats were caused by incomplete electromechanical integration induced by tissue heterogeneity between myocytes and engrafted MSCs in the infarcted myocardium. Here, we report the development of cardiogenic cells from rat MSCs activated by phorbol myristate acetate, a PKC activator, that exhibited high expressions of cardiac-specific markers and Ca(2+) homeostasis-related proteins and showed adrenergic receptor signaling by norepinephrine. Histological analysis showed high connexin 43 coupling, few inflammatory cells, and low fibrotic markers in myocardium implanted with these phorbol myristate acetate-activated MSCs. Infarct hearts implanted with these cells exhibited restoration of conduction velocity through decreased tissue heterogeneity and improved myocardial contractility. These findings have major implications for the development of better cell types for electromechanical integration of cell-based treatment for infarcted myocardium.
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/92669
DOI
10.1073/pnas.1015873107/-/DCSupplemental
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Medical Research Center (임상의학연구센터)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원)
Yonsei Authors
김일권(Kim, Il Kwon) ; 박준희(Park, Jun-Hee) ; 송병욱(Song, Byeong Wook) ; 이문형(Lee, Moon Hyoung) ; 이세연(Lee, Se Yeon) ; 이창연(Lee, Chang Yeon) ; 이충근(Lee, Chung Keun) ; 임소연(Lim, So Yeon) ; 장양수(Jang, Yang Soo) ; 장우철(Chang, Woo Chul) ; 차민지(Cha, Min Ji) ; 최은미(Choi, Eun Mi) ; 최은주(Choi, Eun Ju) ; 함온주(Ham, On Ju) ; 황기철(Hwang, Ki Chul) ; 황혜진(Hwang, Hye Jin)
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