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

Abstract

The efficacy of transplantation of default human marrowderived 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 lM 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 5 30) or without pioglitazone (BM; n 5 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% 6 0.2% n 5 47 vs. 39.5% 6 4.7% n 5 13, p < .05). Transplantation of pioglitazone pretreated MSCs significantly improved change in left ventricular % fractional shortening (BM; 24.8% 6 2.1%, vs. p-BM; 5.2% 6 1.5%). Immunohistochemistry revealed significant improvement of cardiomyogenic transdifferentiation in p-BM in vivo (BM; 0% 6 0% n 5 5, vs. p-BM; 0.077% 6 0.041% n 5 5). Transplantation of pioglitazonepretreated MSCs significantly improved cardiac function and can be a promising cardiac stem cell source to expect cardiomyogenesis.

Exendin-4 Pretreated Adipose Derived Stem Cells Are Resistant to Oxidative Stress and Improve Cardiac Performance via Enhanced Adhesion in the Infarcted Heart

“…Recent evidences suggested that exposure to exogenous hydrogen peroxide (H 2 O 2 ) could increase ROS formation in ADSCs and attenuated cell adhesion, whereas the use of ROS scavengers, such as antioxidant, can reverse the impaired adhesion mediated by integrin [9], [10]. Previously, several approaches have been developed to enhance transplanted cell survival in ischemic myocardium through increasing their adhesive ability, including pretreatment before transplantation and genetically engineering [11], [12], [13]. For example, Laflamme et al .…”

Cord Lining-Mesenchymal Stem Cells Graft Supplemented with an Omental Flap Induces Myocardial Revascularization and Ameliorates Cardiac Dysfunction in a Rat Model of Chronic Ischemic Heart Failure

“…Cardiomyogenic differentiation of BM-MSC has been reported in both allogeneic 22,28 and xenograft models. 29,30 Toma et al found that human BM-MSC injected into healthy SCID/beige adult mice hearts underwent cardiomyogenic differentiation. 29 In vitro studies suggest that a cell-to-cell direct contact between resident cells and BM-MSC is critical in MSC differentiation into cardiomyocytes or smooth muscle cells.…”

Reawakening Atlas: Chemical Approaches To Repair or Replace Dysfunctional Musculature

“…However, surviving MSCderived cardiomyocytes were rare, suggesting that these improvements in cardiac function may be caused by factors secreted from the transplanted cells, which could produce antiapoptotic effects or inhibit post left ventricular remodeling after MI. 64 A most interesting finding from the study was that oral pioglitazone treatment significantly increased the number of surviving, transplanted cells and blood vessel formation in the infarction zone. Although the precise mechanism of orally delivered pioglitazone on transplanted MSC-derived cardiomyocytes was unknown, and cardiac parameters were not improved compared to transplantation with MSC-derived cardiomyocytes alone, this study does show the potential for small molecule methods to enhance tissue-specific stem cell transplantation into cardiomyocytes and influence the cardiac cellular environment post-MI.…”