Improvement of the survival and therapeutic effects of implanted mesenchymal stem cells in a rat model of coronary microembolization by rosuvastatin treatment

摘要

OBJECTIVE: As the impairment of myocardial micro-environments with local inflammatory reactions due to coronary micro-embolization (CME) reduces the survival of transplanted stem cells (SCs). We hypothesized that rosuvastatin treatment could improve the SC survival and enhance their therapeutic effects. MATERIALS AND METHODS: Rat bone marrow-derived mesenchymal stem cells (BMSCs) were infected with lentivirus carrying the green fluorescent protein (GFP) gene. To develop a CME model, rats were injected with a suspension of microthrombotic particles (MTPs) into the left ventricle to obstruct the ascending aorta. GFP-BMSCs were injected with MTPs simultaneously. Rosuvastatin treatment was started 7 days before BMSC transplantation and ended 7 days after transplantation. RESULTS: Expressions of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) were examined by the molecular methods. GFP-positive BMSCs were detected by fluorescence staining. Neovascularization was determined by immunohistochemistry. Myocardial morphology was identified by H&E and Masson’s trichrome staining. Cardiac function was quantified by echocardiography. Three days after CME, the multifocal myocardial necrosis with extensive infiltration of inflammatory cells was observed, accompanied by high expression of TNF-α and IL-1β. Rosuvastatin treatment reduced the infiltration of inflammatory cells and TNF-α and IL-1β expression. 28 days after transplantation, BMSC therapy with rosuvastatin promoted the survival of implanted cells by ≈45-fold while compared with BMSC therapy alone. BMSC therapy with rosuvastatin (instead of BMSC therapy alone) upregulated the VEGF and bFGF expression, increased the capillary density and improved the cardiac function. CONCLUSIONS: These data suggested that rosuvastatin treatment promoted the survival of transplanted SCs and enhanced their therapeutic effects for CME.