Transplantation of Nanoparticle Transfected Skeletal Myoblasts Overexpressing Vascular Endothelial Growth Factor-165 for Cardiac Repair

Abstract

Background— We investigated the feasibility and efficacy of polyethylenimine (PEI) based human vascular endothelial growth factor-165 (hVEGF 165 ) gene transfer into human skeletal myoblasts (HSM) for cell based delivery to the infarcted myocardium. Methods and Results— Based on optimized transfection procedure using enhanced green fluorescent protein (pEGFP), HSM were transfected with plasmid-hVEGF 165 (phVEGF 165 ) carried by PEI (PEI- phVEGF 165 ) nanoparticles. The transfected HSM were characterized for transfection and expression of hVEGF 165 in vitro and transplanted into rat heart model of acute myocardial infarction (AMI): group-1=DMEM injection, group-2= HSM transplantation, group-3= PEI-phVEGF 165 –transfected HSM (PEI-phVEGF 165 myoblast) transplantation. A total of 48 rats received cyclosporine injection from 3 days before and until 4 weeks after cell transplantation. Echocardiography was performed to assess the heart function. Animals were sacrificed for molecular and histological studies on the heart tissue at 4 weeks after treatment. Based on optimized transfection conditions, transfected HSM expressed hVEGF 165 for 18 days with >90% cell viability in vitro. Apoptotic index was reduced in group-2 and group-3 as compared with group-1. Blood vessel density (×400) by immunostaining for PECAM-1 in group-3 was significantly higher ( P =0.043 for both) as compared with group-1 and group-2 at 4 weeks. Regional blood flow (ml/min/g) in the left ventricular anterior wall was higher in group-3 ( P =0.043 for both) as compared with group-1 and group-2. Improved ejection fraction was achieved in group-3 (58.44±4.92%) as compared with group-1 ( P =0.004). Conclusion— PEI nanoparticle mediated hVEGF 165 gene transfer into HSM is feasible and safe. It may serve as a novel and efficient alternative for angiomyogenesis in cardiac repair.