Regulation factors exploring for bone marrow mesenchymal stem cells transdifferentiate into cardiomyocytes

Abstract

OBJECTIVE In order to understand the effects of cardiac microenvironment on the differentiation of Bone marrow mesenchymal stem cells (BMSCs) into cardiomyocyte-like cells (CLCs), the cardiac microenvironment was simulated in vitro by coculturing BMSCs with myocardial cells. METHODS BMSCs were isolated from human bone marrow and their phenotypes were identified with fluorescence-activated cell sorting (FACS). BMSCs were cocultured with neonatal rat ventricular myocytes by semipermeable membrane. This membrane allows the diffusion of secreted factors but prevents physical contact between the two cell populations. The transformation of BMSCs was confirmed by immunocytochemistry, RT-PCR and western blot analysis. The differential expression factors was analysed by gene chip. RESULTS After cocultured with myocytes, SERCA2, RyR2 and GATA-4 mRNA in BMSCs were increased significantly. Some BMSCs became sarcomeric alpha-actinin, desmin, cTnT, and cTnI positive cells, suggesting a developing cardiomyocyte phenotype. Gene chip showed that there were 532 genes upregulated and 325 genes down-regulated after coculturing. Many of these upregulated genes were transcription factor for promoting cardiomyogenesis and some genes encoded cardiac specific proteins. CONCLUSION These results showed that human BMSCs possesses the potential to differentiate into cardiomyocytes, and this process is independent of physical contact between BMSCs and myocytes. On-going investigations may lead to the discovery of mediators of BMSCs migration and differentiation that, in turn, will be more effective way to repair the injured heart. (This work was supported by grants from National Natural Science Foundation of China, No.30271287, 30571850)