Autologous Mesenchymal Stem Cells Transplantation To Treat Dilated Cardiomyopathy In Rabbit

Objective: Recent studies have suggested benefits of mesenchymal stem cells (MSCs) transplantation for the regeneration of cardiac tissue and improve function of regionally infracted myocardium, but its effects on global heart failure is still little known. This study was designed (1) To study the feasibility of establishment a rabbit of adriamycin-induced dilated cardiomyopathy (DCM), (2) To evaluate the survival and the differentiation of MSCs in DCM in rabbits, and the effect of the implanted cells on heart function.Methods: 46 animals were randomly divided into transplanted group, control group and sham group. After isolation and culture of MSCs of transplanted group, Cardiomyopathy was induced by chronic intravenous injection of ADR (total dose 16 mg/kg) in transplanted group, control group. Autologous MSCs labeled with bromodeoxyuridine (Brdu) or equivalent volume of culture medium was intramyocardial injected into the transplanted group and control group, and ADR-free rabbits as sham group underwent surgery but not transplantation. Four weeks after transplantation, function was assessed by echocardiography and hemodynamics. Then hearts were harvested and the implanted sites were analyzed by immunofluorescence to assess the survival and differentiation of implanted MSCs.Results: Four weeks after transplantation, left ventricular systolic diameters (Ds), end-diastolic diameters (Dd) and left ventricular end-diastolic pressure (LVEDP) were increased, left ventricular ejection fraction (EF), left ventricular systolic pressure (LVSP) and maximal rate of left ventricular systolic and diastolic pressure (±dP/dt_max) were decreased in the transplanted group and control group in comparison with those in the sham group. Compare to those in the control group, LVSP and EF were increased, LVEDP was decreased in the transplanted group (P<0.05). Cardiac-like cells with BrdU-stained were identified in the implanted sites in the transplanted group hearts, which expressed cardiac troponin T.Conclusions: (1) Chronic administration of intravenous ADR to rabbits harmed systolic and diastolic function of hearts; it is a simple and reliable method to establish amodel of dilated cardiomyopathy and chronic congestive heart failure, (2) The transplanted MSCs differentiate into cardiac-like cells in myocardium of ADR-induced cardiomyopathy and improved left ventricular function.