Experimental Research On Stem Cell Transplantation In The Treatment Of Doxorubicin-induced Dilated Cardiomyopathy

Background Intravenous injection is a non-vulnerable manner for stem cell transplantation. Previous studies showed that in ischemic heart diseases model, intravenously injected stem cells migrate selectively and target damaged heart tissue, and promotes functional recovery, however, no study has being carried out in non-ischemic heart diseases, eg, in dilated cardiomyopathy (DCM). In this study, we tested the hypothesis that intravenous infusion of bone marrow mesenchymal stem cells (BM-MSCs) home in heart and enhance the damaged heart function in a Adriamycin-induced DCM rat model.Methods and Materials Lewis rats were randomly grouped into intramyocardial injection, single intravenous infusion, double intravenous infusion and sham groups. ADR (2.5 mg/kg, 6 times for 2 weeks) was administered intraperitoneally in all rats for achieving DCM. The intravenous infusion and intramyocardial injection of BM-MSCs were performed. 4 weeks later, serum BNP was measured with the market available kit. Cardiac function was evaluated by echocardiogram and cardiac catheterization. The tissue capillary vessel density was counted by the endothelial CD31 positive cells. Vessle endothelial growth fator (VEGF) mRNA and protein expression were evaluated by RT-PCR and Western blot detect. The injected BM-MSCs were pre-labelled with 5-BrdU before transplantation and were traced by immunofluorescent detect. Results ADR caused a significant deterioration of left ventricular function. Both intramyocardial injection and double intravenous infusion significantly inhibited the dilation of DCM hearts, enhanced the heart function (FS% and EF % increased). Hemodynamics analyse revealed that considerable increase of LVSP and +dp/dt max and decrease of LVEDP in the intramyocardial injection group and the double intravenous infusion group. These two groups showed similar capillary vessel density as well as serum BNP level. Singal intravenous infusion sligntly influenced the serum BNP level and capillary vessel density, however, significantly increased the +dp/dt. Immunofluorescent detect revealed that the injected BM-MSCs distributed globally in the intravenous infusion group. The expression of cardiac specific protein marker indicated the transdifferentiation of grafted cell to cardiac-like cells in transplantation groups.