Transplantation of nanoparticle transfected skeletal myoblasts overexpressing vascular endothelial growth factor-165 for cardiac repair

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 (x400) 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.