Experimental Study On The Effects Of Combining Mesenchymal Stem Cell Transplantation With Erythropoietin For The Improvement Of Cardiac Function After Myocardial Infarction

OBJECTIVES: To assess the effects of mesenchymal stem cell (MSC) transplantation combined with erythropoietin (EPO) administration in the acute period after myocardial infarction on the changes of inflammatory cytokines, left ventricular (LV) remodeling and cardiac function , and investigate the possible mechanisms.METHODS: After the models of myocardial infarction were established, 20 healthy Taihu Meishan swines were randomly divided into four groups : myocardial infarction (control) group, EPO group, MSC group and MSC + EPO group. MSC(1×107 cells) were implanted into coronary artery(MSC and MSC-EPO groups). EPO (1,000 U/kg body weight) was administered by injection subcutaneously 3 times a week for 4weeks (EPO and MSC-EPO groups ). Control group was injected saline solution in the same time period. In each group serum concentration of TNF-αand IL-1βwere detected at different time points after MI, and echocardiography was performed meanwhile. Four weeks after cells transplantation, expressions of MMP-2 and MMP-9 proteins were detected by immunohistochemistry and western blot respectively, and capillary density was counted by immunohistochemistry.RESULTS: Compared with other two groups, concentration of TNF-αand IL-1βin EPO group and MSC+MSC group decreased obviously at the different time points,. When Compared with the control group, the following changes were observed in the EPO group and MSC+EPO group: LV end-diastolic diameter (LVEDD), LV end-systolic diameter (LVESD) and posterior wall thickness (PWT) were decreased, LV ejection fraction (LVEF) was increased, the expressions of MMP-2 and MMP-9 proteins were inhibited and capillary density was enhanced, but there were no differences between MSC group and control group. Furthemore, the benefit in MSC+EPO group is more effective than in EPO group.CONCLUSIONS: 1. EPO treatment can inhibit the inflammation response in acute period after MI. 2. Combination of mesenchymal stem cell transplantation with EPO treatment in acute period after MI results in better improvement of cardiac function and angiogenesis and attenuation of left ventricular remodeling than either of the monotherapy. 3. EPO enhances the beneficial effect of MSC transplantation, which may result from an inhibition of the inflammatory response.