title: Pretreatment of human mesenchymal stem cells with pioglitazone improved efficiency of cardiomyogenic transdifferentiation and cardiac function.
abstract: 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.
authors: Department of Cardiology, Keio University School of Medicine, Tokyo, Japan.
authors: Daisuke
authors: D
authors: Shinmura
authors: Ikuko
authors: I
authors: Togashi
authors: Shunichiro
authors: S
authors: Miyoshi
authors: Nobuhiro
authors: N
authors: Nishiyama
authors: Naoko
authors: N
authors: Hida
authors: Hiroko
authors: H
authors: Tsuji
authors: Hikaru
authors: H
authors: Tsuruta
authors: Kaoru
authors: K
authors: Segawa
authors: Yuiko
authors: Y
authors: Tsukada
authors: Satoshi
authors: S
authors: Ogawa
authors: Akihiro
authors: A
authors: Umezawa
mesh_terms: D000328:Adult; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation / Q000187:drug effects*; D054338:Cell Transdifferentiation; D002478:Cells, Cultured; D006321:Heart / Q000503:physiopathology; D006352:Heart Ventricles / Q000503:physiopathology*; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects*; D009203:Myocardial Infarction / Q000503:physiopathology / Q000628:therapy; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D047495:PPAR gamma / Q000378:metabolism; D000077205:Pioglitazone; D051381:Rats; D011923:Rats, Nude; D045162:Thiazolidinediones / Q000494:pharmacology*; D016277:Ventricular Function, Left
chemical_list: D047495:PPAR gamma; D045162:Thiazolidinediones; D000077205:Pioglitazone