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

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

Research output: Contribution to journalArticlepeer-review

35 Citations (Scopus)

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 Ca2+ 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.

Original languageEnglish
Pages (from-to)296-301
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number1
DOIs
Publication statusPublished - 2011 Jan 4

All Science Journal Classification (ASJC) codes

  • General

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