Vascular Endothelial Growth Factor (VEGF165) Plus Basic Fibroblast Growth Factor (bFGF) Producing Cells induce a Mature and Stable Vascular Network—a Future Therapy for Ischemically Challenged Tissue

BackgroundVascular endothelial growth factor (VEGF)165 induces formation of immature blood vessels with increased permeability. In this study, we used a cell-based gene-transfer model of fibroblasts to investigate the effects of a combined in vivo treatment consisting of the VEGF165 and basic fibroblast growth factor (bFGF) proteins on ischemic and non-ischemic tissues.Materials and MethodsAfter controlled in vitro adenoviral transfection we transplanted fibroblasts into either healthy tissue, or into an ischemic skin flap model at different tissue locations and at different time points. Subsequent protein expression and angiogenic effects were measured using ELISA, PCR, immunohistology, planimetry, and microangiography.ResultsTransfected fibroblasts temporarily produced VEGF165 and bFGF. After transdermal implantation we found an up-regulation of genes encoding for both factors in tissue samples. The combined transplantation of VEGF165 and bFGF modified cells increased the number of sm-actin+/CD31+ blood vessels and reduced necrosis by 25%. The number of functional blood vessels increased over a period of 168 d even in healthy tissue.ConclusionsWe achieved stable vessel growth in healthy tissue by inducing a temporary overexpression of VEGF165 and bFGF and improved the survival of ischemic tissue. One possible mechanism for the latter observation is the stabilization of VEGF165-induced hyperpermeable vessels by a bFGF-mediated pericytial recruitment of smooth muscle cells.