Treatment of Human Mesenchymal Stem Cells with Angiotensin Receptor Blocker Improved Efficiency of Cardiomyogenic Transdifferentiation and Improved Cardiac Function via Angiogenesis

Abstract

To improve the modest efficacy of mesenchymal stem cell (MSC) transplantation, the treatment of human MSCs with angiotensin receptor blockers (ARBs) was investigated. MSCs were cultured with or without the medium containing 3 μmol/l of ARBs before cardiomyogenic induction. After cardiomyogenic induction in vitro, cardiomyogenic transdifferentiation efficiency (CTE) was calculated by immunocytochemistry using anticardiac troponin-I antibody. In the nude rat chronic myocardial infarction model, we injected MSCs pretreated with candesartan (A-BM; n = 18) or injected MSCs without pretreatment of candesartan (BM; n = 25), each having survived for 2 weeks. The left ventricular function, as measured by echocardiogram, was compared with cardiomyogenic transdifferentiation in vivo, as determined by immunohistochemistry. Pretreatment with ARBs significantly increased the CTE in vitro (10.1 ± 0.8 n = 12 vs. 4.6 ± 0.3% n = 25, p < .05). Transplantation of candesartan-pretreated MSCs significantly improved the change in left ventricular ejection fraction (BM; -7.2 ± 2.0 vs. A-BM; 3.3 ± 2.3%). Immunohistochemistry revealed significant improvement of cardiomyogenic transdifferentiation in A-BM in vivo (BM; 0 ± 0 vs. A-BM; 0.014 ± 0.006%). Transplantation of ARB-pretreated MSCs significantly improved cardiac function and can be a promising cardiac stem cell source from which to expect cardiomyogenesis.