Targeted delivery of vascular endothelial growth factor to enhance the stem cell therapy in treating myocardial infarction in rats

The stem cell therapy to treat myocardial infarction (MI) has shown disappointed results largely due to the poor survival of transplanted stem cells in the MI region. We propose a combination therapy by targeted delivery of a proangiogenic compound, vascular endothelial growth factor (VEGF), to MI region to improve the micro-environment, which may enhance the survival of transplanted stem cells, and further improve the cardiac function. In this study, P-selectin conjugated immunoliposomes containing VEGF were given to the MI rats through tail vein injection immediately after surgery. Mesenchymal stem cells (MSCs) were transplanted to the MI region one week later. Left ventricular percent fractional shortening were measured 1 week and 4 weeks post MI using echocardiography. Results indicate that MI rats with no treatment lost 8% contractility (~40% of its heart function) from 1 week to 4 weeks post-MI. Either targeted VEGF or MSCs treatment alone can slow down the loss by half to 4%. The combination of targeted VEGF and MSCs treatment further decreased the contractility loss to 0.7%. In conclusion, the combination treatment of targeted VEGF and MSCs results in a larger recovery in cardiac function compared to either targeted VEGF or stem cell treatment alone.