title: 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.
abstract: BACKGROUND
  Vascular 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.
  
  
  METHODS
  After 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.
  
  
  RESULTS
  Transfected fibroblasts temporarily produced VEGF(165) and bFGF. After transdermal implantation we found an up-regulation of genes encoding for both factors in tissue samples. The combined transplantation of VEGF(165) 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.
  
  
  CONCLUSIONS
  We achieved stable vessel growth in healthy tissue by inducing a temporary overexpression of VEGF(165) and bFGF and improved the survival of ischemic tissue. One possible mechanism for the latter observation is the stabilization of VEGF(165)-induced hyperpermeable vessels by a bFGF-mediated pericytial recruitment of smooth muscle cells.
authors.affiliation: Department of Plastic and Hand Surgery, Burn Care Center, Institute for Research in Operative Medicine (IFOM), University Hospital Witten/Herdecke, Campus Cologne, Germany. timo@spanholtz.net
authors.forename: Timo A
authors.initials: TA
authors.lastname: Spanholtz
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Theodorou
authors.forename: Thomas
authors.initials: T
authors.lastname: Holzbach
authors.forename: Sebastian
authors.initials: S
authors.lastname: Wutzler
authors.forename: Riccardo E
authors.initials: RE
authors.lastname: Giunta
authors.forename: Hans-Guenther
authors.initials: HG
authors.lastname: Machens
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002478:Cells, Cultured; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000235:genetics*; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology / Q000637:transplantation*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D006085:Graft Survival / Q000502:physiology; D007511:Ischemia / Q000628:therapy*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000098:blood supply; D013524:Surgical Flaps / Q000098:blood supply; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D016222:Fibroblast Growth Factor 2