EXPRESSION OF HEART DEVELOPMENT-ASSOCIATED GENES IN MESENCHYMAL STEM CELLS CO-CULTURED WITH CARDIOMYOCYTES

摘要

Recent studies have demonstrated that bone marrow mesenchymal stem cells (MSCs) have the potential to transdifferentiate into cardiomyocytes (CMs) in an appropriate condition both in vivo and in vitro. However, there exists a controversy among a variety of studies about whether MSCs can differentiate into CMs without physical contacts with CMs, and the molecular signals that underlie this process are not fully understood. In the present study, MSCs were cocultured with CMs in a dual chamber dish separated by a semipermeable membrane for 2 weeks. During this non-direct contact coculture procedure, cardiomyogenic differentiation and relative genes expression in MSCs were evaluated. After coculture with CMs, MSCs showed a stick-like or elliptical morphology. Immunofluorescent stain results revealed that α-actin and cardiac troponin T(cTnT) positive cells were found in MSCs at 5 days after coculture with CMs. Results from RT-PCR demonstrated the expression level of TGF-β, Nkx-2.5, GATA-4 and MEF-2C genes began to increase at 1 day and reached the peak at 7 days after coculture. In conclusion, non-direct contact with CMs (1:5) is conducive for MSCs to differentiate into CMs in vitro, and TGF-β, Nkx-2.5, GATA-4 and MEF-2C genes may play a crucial role during the transdifferentiation.