The Role of Vascular Endothelial Growth Factor in Mechanically Stimulated Muscle Derived Stem Cell Repair

Abstract

We have previously shown that muscle‐derived stem cells (MDSCs) are significantly better than myoblasts at maintaining cardiac function after infarction, which is likely due to higher survival and vascular endothelial growth factor (VEGF) secretion. Mechanical stimulation increases VEGF secretion, and after mechanically preconditioning MDSCs and injecting them into an acute model of cardiac infarction function is improved. Therefore, we hypothesized that the benefits seen from mechanical stimulation is due to an increase in VEGF, and if we block VEGF we will not see an improvement in repair. To test this we have mechanically stimulated MDSCs transduced with the soluble VEGF receptor antagonist sFlt1 and tested their regenerative potential in the skeletal muscle of a mouse model of Duchene Muscular Dystrophy. We have found that mechanically stimulating MDSCs resulted in an increase in angiogenesis in the engraftment area. The MDSCs transduced with sFlt1 resulted in less angiogenesis, and the mechanically stimulated MDSCs transduced with sFlt1 showed no difference in angiogenesis from the un‐stimulated sFlt1 group. There also appears to be little difference between fibrosis in the sFlt1 stimulated and un‐stimulated groups. Therefore, VEGF appears to be a critical factor in angiogenesis following cell transplantation in mechanically stimulated MDSCs.Grant Funding Source : DOD