title: Adenovirus vector-mediated transfer of the vascular endothelial growth factor cDNA to healing abdominal fascia enhances vascularity and bursting strength in mice with normal and impaired wound healing.
abstract: BACKGROUND
  We hypothesized that adenovirus-mediated transfer of the vascular endothelial growth factor (VEGF121) complementary DNA (cDNA) to murine laparotomy fascial wounds would enhance vascularity and bursting strength.
  
  
  METHODS
  Microfibrillar collagen sponges saturated with adenovirus (Ad) vectors encoding for the human VEGF121 cDNA (Ad(CU)VEGF121.1), a control marker gene (Ad beta gal, AdLuc) or no transgene (AdNull) were sutured to fascial edges during laparotomy closure in normal mice and mice treated with dexamethasone. Endpoints addressed included transgene expression in the fascia and surrounding tissue, the number of blood vessels in the healing wound determined using immunostaining, and wound bursting strength using a calibrated tensinometer.
  
  
  RESULTS
  Transgene expression was detected readily in the fascial edges, but only marginally detectable in neighboring tissues. In normal mice and mice treated with dexamethasone, no differences were observed at 7 days. Strikingly, however, 21 days after wound closure/therapy, significantly more blood vessels were present in the wounds that received the VEGF121 vector compared with controls (normal: AdNull: 4.2 +/- 1.8; Ad(CU)VEGF121.1: 11.2 +/- 1.2; P <.05; dexamethasone: AdNull: 1.4 +/- 0.8; Ad(CU)VEGF121.1: 5.4 +/- 1.2; P <.05), and bursting strength was significantly higher in VEGF121-treated wounds (normal: AdNull: 665 +/- 68 mN/mm; Ad(CU)VEGF121.1: 956 +/- 82 mN/mm; P <.0005; dexamethasone: AdNull: 234 +/- 111 mN/mm; Ad(CU)VEGF121.1: 592 +/- 121 mN/mm; P <.03).
  
  
  CONCLUSIONS
  Adenovirus-mediated gene transfer to healing fascial wounds is achieved readily using a microfibrillar collagen sponge, with transfer of the human VEGF121 cDNA significantly enhancing wound vascularity and bursting strength in normal mice, as well as in mice treated with dexamethasone.
authors.affiliation: Thoracic Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors.forename: Maneesh
authors.initials: M
authors.lastname: Ailawadi
authors.forename: Jay M
authors.initials: JM
authors.lastname: Lee
authors.forename: Sang
authors.initials: S
authors.lastname: Lee
authors.forename: Neil
authors.initials: N
authors.lastname: Hackett
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Crystal
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Korst
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D018076:DNA, Complementary / Q000008:administration & dosage*; D003907:Dexamethasone / Q000494:pharmacology; D016228:Endothelial Growth Factors / Q000235:genetics*; D005205:Fascia / Q000378:metabolism; D005260:Female; D022761:Gene Transfer, Horizontal; D015316:Genetic Therapy; D007813:Laparotomy; D008222:Lymphokines / Q000235:genetics*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014945:Wound Healing
chemical_list: D018076:DNA, Complementary; D016228:Endothelial Growth Factors; D008222:Lymphokines; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D003907:Dexamethasone