Nanoparticle based delivery of hypoxia-regulated VEGF transgene system combined with myoblast engraftment for myocardial repair

Abstract A regulated promoter system to control gene expression is desirable for safe and efficacious over-expression of therapeutic transgene. Combined with skeletal myoblast (SkMs), we report the efficacy of hypoxia-regulated VEGF gene delivery for myocardial repair during acute myocardial infarction (AMI). A hypoxia-regulated VEGF plasmid (pHRE-VEGF) was developed. After optimization, ∼30% SkMs were transfected using polyethyleneimine (PEI) nanoparticles. The peak VEGF expression was higher in pHRE-VEGF transfected SkMs ( VEGF SkMs) under hypoxia (151.34 ± 8.59 ng/ml) than that with normoxia (16.92 ± 2.74 ng/ml). The efficacy of hypoxia-regulated gene expression system was assessed in a rabbit model of AMI. The animals were grouped to receive basal M199 without cells (group-1) or containing non-transfected SkMs (group-2) or VEGF SkMs (group-3). In group-4, VEGF SkMs were injected into normal heart to serve as normoxia control. Improved SkM survival was observed in group-3 and -4 ( p p p p