Background — Myocardial injury results in contractile dysfunction due to cardiomyocyte loss and progressive replacement by fibroblasts to form scar tissue. The application of bone marrow mesenchymal stem cell (MSC) has the potential to treat the cardiac repair following myocardial injury. MSCs therapy has a limitation due to their poor viability after cell transplantation. To limit cell loss after MSCs transplantation into the infarcted myocardium, we genetically modified MSCs with FGF-2 ex vivo before transplantation. Methods and Results — After 2 weeks culture, MSCs formed colonies with a fibroblast-like morphology, over 95% of MSCs expressed CD71 and 50% of MSCs expressed cardiomyocyte-specific transcription factors, Nkx 2.5 by immunocytochemistry. In hypoxic culture, FGF-2-tranfected MSCs secreted significantly higher levels of FGF-2 into the culture medium than control MSCs transfected with lacZ (2604짹18pg/ml vs. 53짹5pg/ml, respectively, p<0.01). At hypoxic conditions, FGF-2-tranfected MSCs displayed a threefold increase of viable cells, reductions of apoptotic gene, Bcl2 and DNA laddering, compared to MSCs only. Four weeks after cryoinjury of rat hearts and implantation of 1.0 X 106 cells, viable cells labeled with 4���,6-diamidino-2-phenylindole (DAPI) were identified in host myocardium. Survival of FGF-2-transfected MSCs was 60% higher than that of control GFP-transfected MSCs and in the former, expression of cardiac troponin I (CTn I) and voltage-gated Ca2+ channel (CaV2.1) was increased and new blood vessels were significantly formed. Conclusion — Our studies indicate that FGF-2-transfected MSCs delivered into myocardium after cryo-injury survive and continue to display cardiomyocytes characteristics greatly compared to MSCs alone. These data may provide genetic modification of MSCs with a therapeutic gene before transplantation as novel therapeutic rationales for the treatment of myocardial infarction and end-stage cardiac failure.