Transgenic overexpression of VEGF164 enhances topical neoangiogenesis without detectable local or systemic side effects.

Abstract

Various routes of administration have been used for delivering angiogenic genes to ischemic regions. A previous, preliminary study proved the feasibility of in vivo neoangiogenesis stimulation by ex vivo vascular endothelial growth factor (VEGF)-transduced fibroblasts. Taking this into account our aim was to validate therapeutical efficacy of this approach and to investigate potential side effects.Allogenous collagen membranes were implanted at the groin in 30 Wistar rats. Either untransfected, GFP- or VEGF-transfected fibroblasts were injected at the implantation site at the time of surgery. Biopsies were obtained from the membranes, surrounding connective tissue, brain, lung, liver and blood at days 7 and 14 post operation. Samples were investigated for distribution of GFP-positive cells, VEGF-expression, and vessel architecture.Transgenic fibroblasts remained at the site of injection and showed no trafficking into blood or organs. VEGF-overexpression was detectable and resulted in enhanced neovascularization of the membranes. Vessel pathologies were neither detectable in the membrane nor the surrounding tissue.