Synergistic effect between human vascular endothelial growth factor and angiopoietin-1 combined with myoblast therapy for treatment of ischemically damaged hind limbs

Abstract

Therapeutic angiogenesis aimed at improving peripheral blood flow by stimulating the growth and development of collateral vessels through administration of angiogenic growth factors is a potential treatment for peripheral vascular disease. In this study, synergistic interaction between two of these factors a?? vascular endothelial growth factor (VEGF) and angiopoietin-1 a?? in combination with myoblast therapy, was proposed as a promising candidate for improving circulation in a rabbit model of hind limb ischemia. Both VEGF and Ang-1 genes were delivered in a single administration using a novel bicistronic adenoviral vector that was carried in myoblasts. Extensive in vivo survival of transplanted myoblasts was observed in the ischemic limb, with angiographic evidence of enhanced neovascularization in the treated group. This was confirmed by significantly increased vascular density observed at the immunohistochemical level. Simultaneous expression of VEGF and angiopoietin-1 from bicistronic adenoviral vector transduced myoblasts potently stimulated enhanced functional neovascularization in the ischemic limbs.