Open AccessPretreatment of Human Mesenchymal Stem Cells with Pioglitazone Improved Efficiency of Cardiomyogenic Transdifferentiation and Cardiac Function
Author(s) -
Shinmura Daisuke,
Togashi Ikuko,
Miyoshi Shunichiro,
Nishiyama Nobuhiro,
Hida Naoko,
Tsuji Hiroko,
Tsuruta Hikaru,
Segawa Kaoru,
Tsukada Yuiko,
Ogawa Satoshi,
Umezawa Akihiro
Publication year - 2011
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.574
Subject(s) - pioglitazone , transdifferentiation , mesenchymal stem cell , transplantation , in vivo , cardiac function curve , cell therapy , medicine , stem cell , biology , endocrinology , microbiology and biotechnology , heart failure , diabetes mellitus , type 2 diabetes
The efficacy of transplantation of default human marrow‐derived mesenchymal stem cells (MSCs) was modest. In this study, our challenge was to improve the efficacy of MSC transplantation in vivo by pretreatment of MSCs with pioglitazone. MSCs were cultured with or without medium containing 1 μM of pioglitazone before cardiomyogenic induction. After cardiomyogenic induction in vitro, cardiomyogenic transdifferentiation efficiency (CTE) was calculated by immunocytochemistry using anti‐cardiac troponin‐I antibody. For the in vivo experiments, myocardial infarction (MI) at the anterior left ventricle was made in nude rats. Two weeks after MI, MSCs pretreated with pioglitazone (p‐BM; n = 30) or without pioglitazone (BM; n = 17) were injected, and then survived for 2 weeks. We compared left ventricular function by echocardiogram and immunohistochemistry to observe cardiomyogenic transdifferentiation in vivo. Pretreatment with pioglitazone significantly increased the CTE in vitro (1.9% ± 0.2% n = 47 vs. 39.5% ± 4.7% n = 13, p < .05). Transplantation of pioglitazone pretreated MSCs significantly improved change in left ventricular % fractional shortening (BM; −4.8% ± 2.1%, vs. p‐BM; 5.2% ± 1.5%). Immunohistochemistry revealed significant improvement of cardiomyogenic transdifferentiation in p‐BM in vivo (BM; 0% ± 0% n = 5, vs. p‐BM; 0.077% ± 0.041% n = 5). Transplantation of pioglitazone‐pretreated MSCs significantly improved cardiac function and can be a promising cardiac stem cell source to expect cardiomyogenesis. S TEM C ELLS 2011; 29:357–366