Mesenchymal stem cells potentiates Cardiac progenitor cells survival and engraftment after transplantation in myocardial infraction

Abstract

Pluripotent stem cell-derived cardiac progenitor cells (CPCs) can differentiate into cardiomyocytes, endothelial cells and vascular smooth muscle cells in vitro and in vivo without teratoma formation. This potential makes CPC as a prospective cell source to cardimyocyte regeneration. However, the poor cell survival and engraftment after transplanting into an ischemic hostile environment that limit the application potential of CPC for heart repair. We found that mesenchymal stem cells (MSCs) can promote the proliferation and myocardial differentiation of CPCs. Nevertheless, there is little information about mechanisms of these two cellular communication and not clear effects in vivo hybrid application of two types of cell for heart repairs. Since the niche is very important to influence the fates of CPC, we proposal the hypothesis that components of MSC secreted extra cellular matrix play critical role to support Nkx2.5+ CPC survival and proliferation. Fibronectin, a key component of ECM highly enriched in MSC will be focus on this study. In our research process, the ESC-derived GFP+ CPCs are sorted out, labeled, mixed with mouse MSCs or fibronection and injected into infarcted area of the mouse heart. The groups were classified as: A). CPCs group, MSCs group, CPCs + MSCs group; B). CPCs + PBS group, CPCs + fibronection group, fibronection group. After 4 weeks, heart function and the labeled cells’ differentiation of the animal model will be identified. The survival rate of CPCs will also be tested and compared between different groups. By statistical analysis, the heart function, cell survival and cardiac differentiation of injected CPCs will be tested. Our study aims to find a more optimized and effective cell therapy after heart infarction.