Abstract 3260: Improve Cardiac Performance by Pre-differentiated Bone Marrow Mesenchymal Stem Cells in Rat Heart Failure
Cardiac microenvironment can induce bone marrow mesenchymal stem cells (BMSCs) differentiation into cardiac cells like myocytes. We and others have shown previously that BMSCs can be induced into cardiac like cells by cocultured with newly born rat myocytes. In the present study, we assessed whether the transplantation of pre-differentiated BMSCs (pBMSCs) are more effective in treating heart failure than the undifferentiated BMSCs (uBMSCs). After establishing a reproducible rat chronic heart failure (CHF) model with the ligation of the left anterior descending (LAD) coronary artery, BMSCs were injected into borders of cardiac scar tissue 1 wk after experimental ligation. Cardiac performance was evaluated by echocardiography at 1, 2, and 4 wk after pBMSCs or uBMSCs or PBS injection (n=10). Langendorff working-heart and histological studies were performed 4 wk after treatment. Echocardiography revealed a significantly (p<0.01) improved ejection fraction and fractional shortening in the pBMSCs treated group (EF: 78.3±3.39%; FS: 45.62±2.94%) compared to uBMSCs treated group (EF: 54.49±3.58%; FS: 27.79±4.10%) at 4 weeks. Similarly, we observed better coronary flow (CF) pattern in the pBMSCs treated group (CF: 9.43±0.21 ml/min) compared to the uBMSCs treated group (CF: 6.89±0.66 ml/min, P<0.01). Furthermore, we observed a better recovery of +dP/dt, and −dP/dt (P<0.01) in the pBMSCs-treated group compared to uBMSCs-treated group at 4wk after cell transplantation. Immunofluorescence microscopy revealed co-localization of superparamagnetic iron oxide (SPIO)-labeled transplanted cells with cardiac markers. SPIO and MLC2v or cTnT double positive cells were more in pBMSCs group than that in uBMSCs group. This double-labeled myocardium seemed to be structurally integrated with the healthy ventricular wall and had expressed connexion 43 to link with host cardiomyocytes. These data provide strong evidence that pre-differentiation of BMSCs prior to implantation more effective in restoring cardiac function after infarction than the undifferentiated BMSCs. Our findings pave the way to the development of a novel and promising therapeutic strategy to treat heart failure.