Pretreatment of Human Mesenchymal Stem Cells with Pioglitazone Improved Efficiency of Cardiomyogenic Transdifferentiation and Cardiac Function

• Published in: Stem cells (Dayton, Ohio) Vol. 29; no. 2; pp. 357 - 366
• Main Authors: Shinmura, Daisuke, Togashi, Ikuko, Miyoshi, Shunichiro, Nishiyama, Nobuhiro, Hida, Naoko, Tsuji, Hiroko, Tsuruta, Hikaru, Segawa, Kaoru, Tsukada, Yuiko, Ogawa, Satoshi, Umezawa, Akihiro
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.02.2011
• Subjects: Adult; Animals; Bone Marrow Cells - cytology; Cardiac; Cell culture; Cell Differentiation - drug effects; Cell Transdifferentiation; Cell transplantation; Cells, Cultured; Heart - physiopathology; Heart Ventricles - physiopathology; Humans; Immune‐deficient models; Male; Mesenchymal Stem Cell Transplantation - methods; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - drug effects; Myocardial Infarction - physiopathology; Myocardial Infarction - therapy; Myocytes, Cardiac - cytology; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - physiology; PPAR gamma - metabolism; Rats; Rats, Nude; Somatic stem cells; Stem cell plasticity; Thiazolidinediones - pharmacology; Transdifferentiation; Ventricular Function, Left
• ISSN: 1066-5099; 1549-4918
• DOI: 10.1002/stem.574

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. STEM CELLS 2011; 29:357–366