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.
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.
Ailawadi
Maneesh
M
Thoracic Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Lee
Jay M
JM
Lee
Sang
S
Hackett
Neil
N
Crystal
Ronald G
RG
Korst
Robert J
RJ
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
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