Abstract 412: Wnt / β-catenin Inhibitor Differentiates Human Mesenchymal Stem Cells into Myogenic Lineage in vitro and Improved Cardiac Function in vivo in Rat Model of Myocardial Infarction

Abstract

Cardiovascular disease (CVD) is one of the major causes of morbidity and mortality. At present, available therapeutic options for the treatment of cardiovascular diseases are limited and provide solution only to reduce the symptoms of CVD. The indigenous capability of cardiac tissue to meet the degeneration is limited. The feasible option is stem cells based regenerative medicine to repair or regenerate the myocardial cells and restore normal cardiac function. The aim of the present study is to assess the potential of small molecules for the differentiation of MSCs into cardiomyocytes. In this study, MSCs were cultured in vitro and were characterized by immunochemistry, and flow cytometry for the presence of MSCs markers, CD90, CD73, CD44, CD29, and for tri-lineage differentiation. MSCs were treated with wiki-4 for 14 days to induce cardiac differentiation, and were characterized for the presence cardiac markers by gene and protein expression for GATA-4, α-actinin, cTnT, cTnI, and myosin heavy chain, and found positive for these markers. These induced cardiac progenitor cells were transplanted into the infarcted myocardium of rats, where they exhibited increased persistence, engraftment, and homing in the infarcted region, and expressed cardiac markers within the border zone. Transplanted group improved left ventricular wall thickness at 4 weeks post injury, and reduced infarct size. Functional performance of the hearts was analyzed through M-mode echocardiography, which results in significant (p<0.05) improvement in the heart function including left ventricular internal diameter systolic and diastolic, ejection fraction, fractional shortening, end systolic volume and diastolic volume, and stroke volume compared to control. Histological examination of the heart sections 4 weeks post MI showed that MSCs home towards the site of injury. The transplanted cells expressed cardiac markers and contributed to the cardiac tissue recovery. The results of the present study demonstrate that myocytes derived of MSCs enhance the regeneration potential of the infarcted myocardium.