Feasibility of hypoxia inducible factor gene transfer in endothelial progenitor cell for vascular regeneration

AIM To explore whether the overexpression of hypoxia inducible factor-1α(HIF-1α)is beneficial in cell therapy of hypoxia-induced ischemic disease.METHODS Adenovirus mediated human HIF-1(Ad-HIF-1)was transduced in human endothelial progenitor cells(EPC)in vitro.Heterologous EPC transduced with adenovirus encoding HIF-1α were administered to Balb/c nude mice with hindlimb ischemia.RESULTS Augmented EPC proliferative activity and enhanced migration activity were seen in HIF-1 treated EPC(P0.05).and exogenous EPC homing was observed.In vitro HIF-1-transduced EPC contributed to neovascularization in vivo.Limb necrosis reduced by 60% neovascularization in comparison with that in control animals and neovascularization was improved.CONCLUSION In vitro,Ad-HIF-1-EPC gene transfer enhances EPC proliferation and migration.In vivo,gene-modified EPC facilitate the strategy of cell transplantation to augment naturally impaired neovascularization in an animal model of experimentally induced limb ischemia.