Objective To investigate the feasibility of differentiation of umbilical cord-derived mesenchymal stem cells (UC-MSCs) into cardiomyocytes in vitro and the effects of UC-MSCs transplantation on the mouse models of myocardial infarction.MethodsUC-MSCs were induced by 10 μmol/L 5-aza for 14 days in vitro and then identified by RT-PCR and immunofluorescence staining. The mouse models of myocardial infarction were developed by intraperitoneal injection of isoproterenol hydrochloride (ISO) 3.0 mg/(kg/d). After 48 h, DAPI-labeled UC-MSCs were transplanted via the tail vein twice within 48 to 72 hours in the experimental group. At 4 and 8 weeks after transplantation, the mouse heart and spleen of both groups were taken out. The cardiac index and spleen index of the mouse models were measured, and the differentiation in vivo and the repair of cardiomyocyte injury were evaluated histologically using immunofluorescence and basic fuchsin-picric acid (HBFP) staining, with the mouse models of myocardial injury without UC-MSCs transplantation as control. ResultsRT-PCR analysis showed that the induced cells expressed cardiac-specific genes α-actin, TBX5, GATA4 and NKx2.5. In addition, immunofluorescence staining showed that the induced cells were positive for α-actin and NKx2.5, and some cells showed double nuclei. The models with UC-MSC transplantion were found to have DAPI-positive cardiac cells migrated to the myocardium and showed cardiac α-actin positive at 4 weeks and 8 weeks after transplantation. Obvious therapeutic effect was shown by HBFP staining and by the heart and spleen indexes after UC-MSC transplantation in the myocardial injury mouse models. Conclusions5-azainduced UC-MSCs can be directed to differentiate into cardiomyocytes in vitro, and significant therapeutic effect on the mouse myocardial injury in vivo can be obtained through UC-MSCs transplantation via the tail vein.