BACKGROUND: Recent studies have shown that bone marrow-derived stem cells 
differentiate into the phenotype of cardiomyocytes in vivo and in vitro. We 
tried to regenerate infarcted myocardium by implanting ex vivo transforming 
growth factor (TGF)-beta-preprogrammed CD117 (c-kit)-positive (CD117+) stem 
cells intramyocardially.
METHODS AND RESULTS: CD117+ cells were isolated from the bone marrow mononuclear 
cells of GFP-transgenic or normal C57/BL6 mice. The myogenic differentiation of 
CD117+ cells was achieved by cultivation with TGF-beta. Using an acute 
myocardial infarction model, we also tried to regenerate infarcted myocardium by 
implanting untreated (newly isolated) or preprogrammed (24 hours of cultivation 
with 5 ng/mL TGF-beta1) CD117+ cells intramyocardially. TGF-beta increased the 
cellular expression of myosin, troponins, connexin-43, GATA-4, and NKx-2.5, 
which suggested that it induced the myogenic differentiation of CD117+ cells. 
Compared with the effects of PBS injection only, the microvessel density in the 
infarcted myocardium was increased significantly 3 months after the implantation 
of either TGF-beta-preprogrammed or untreated CD117+ cells. Moreover, many of 
the TGF-beta-preprogrammed CD117+ cells were stained positively for myosin, 
whereas few of the untreated CD117+ cells were. Histological analysis revealed 
newly regenerated myocardium in the left ventricular anterior wall after the 
implantation of TGF-beta-preprogrammed cells but not untreated cells. 
Furthermore, the left ventricular percent fraction shortening was significantly 
higher after the implantation of TGF-beta-preprogrammed cells than after the 
implantation of untreated CD117+ cells.
CONCLUSIONS: TGF-beta conducted the myogenic differentiation of CD117+ stem 
cells by upregulating GATA-4 and NKx-2.5 expression. Therefore, the 
intramyocardial implantation of TGF-beta-preprogrammed CD117+ cells effectively 
assisted the myocardial regeneration and induced therapeutic angiogenesis, 
contributing to functional cardiac regeneration.