Phorbol myristate acetate differentiates human adipose-derived mesenchymal stem cells into functional cardiogenic cells.
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.
Institute of Catholic Integrative Medicine, Incheon St. Mary's Hospital, The Catholic University of Korea College of Medicine, Incheon 403-720, Republic of Korea.
Woochul
W
Chang
Soyeon
S
Lim
Byeong-Wook
BW
Song
Chang Youn
CY
Lee
Moon-Seo
MS
Park
Young-An
YA
Chung
Cheesoon
C
Yoon
Se-Yeon
SY
Lee
Onju
O
Ham
Jun-Hee
JH
Park
Eunhyun
E
Choi
Lee-So
LS
Maeng
Ki-Chul
KC
Hwang
D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects*; D017202:Myocardial Ischemia / Q000628:therapy; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000637:transplantation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration / Q000235:genetics; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D013755:Tetradecanoylphorbol Acetate