Bone marrow-derived mesenchymal stem cells (MSCs) have been proposed as a promising source for cellular cardiomyoplasty after heart infarction because of their high plasticity and good availibility. We have isolated bone marrow from transgenic mice expressing EGFP and culture-expanded MSCs. The cells showed typical MSC markers, differentiated into osteocytes and adipocytes in vitro and generated to a small extent muscle-like cells after exposure to 5-azacytidine. MSCs were injected into infarcted hearts of syngeneic wild type mice (n = 50) and their fate determined 1 to 19 weeks postoperatively. Prominent long term engraftment of EGFP positive MSCs was observed. However, morphological and immunohistochemical analysis did not reveal transdifferentiation into cardiomyocytes or endothelial cells whereas calcifications and bone formation was detected in a large number of mice. Thus, the local microenvironment does not restrict the fate of the transplanted MSCs.