Transplantation of induced bone marrow mesenchymal stem cells improves the cardiac function of rabbits with dilated cardiomyopathy via upregulation of vascular endothelial growth factor and its receptors

Bone marrow mesenchymal stem cells (BMMSCs) have shown promise in repairing injured myocardium. However, few studies have explored the potential of BMMSC transplantation for dilated cardiomyopathy (DCM). In this study we aimed to examine whether BMMSC transplantation improves the cardiac function of dilated cardiomyopathy and investigate the underlying mechanism. We established a DCM model in rabbit, then transplanted BMMSCs induced by 5-azacytidine into the rabbit, and determined the left ventricular pressure and the expression of vascular endothelial growth factor (VEGF) and its receptors. Immunohistochemisty, ultrastructural and reverse transcription polymerase chain reaction (RT-PCR) analysis proved that 5-azacytidine induced the differentiation of BMMSCs into cardiomyocyte-like cells. Upon transplantation of the induced BMMSCs into a DCM model, significantly higher maximum rates of rise and decline (+/- dp/dt) of left ventricular pressure and left ventricular systolic pressure, as well as much lower left ventricular diastolic pressure, were observed compared with the control group (P < 0.05). After four weeks, deposition of collagen fibers in the myocardium of transplantation group was reduced, accompanied by increased expression of VEGF and its receptors as detected by RT-PCR. Taken together, our results suggest that BMMSC transplantation could alleviate DCM through angiogenesis via the upregulation of VEGF and its receptors.