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 Journal Article

  

Authors:	Ailawadi, M.; Lee, J. M.; Lee, S.; Hackett, N.; Crystal, R. G.; Korst, R. J.
Article 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 CUVEGF121.1), a control marker gene (Adβgal, 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 CUVEGF121.1: 11.2 ± 1.2; P < .05; dexamethasone: AdNull: 1.4 ± 0.8; Ad CUVEGF121.1: 5.4 ± 1.2; P < .05), and bursting strength was significantly higher in VEGF121-treated wounds (normal: AdNull: 665 ± 68 mN/mm; Ad CUVEGF121.1: 956 ± 82 mN/mm; P < .0005; dexamethasone: AdNull: 234 ± 111 mN/mm; Ad CUVEGF121.1: 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.
Keywords:	immunohistochemistry; vasculotropin; controlled study; treatment outcome; vascular endothelial growth factor a; nonhuman; laparotomy; mouse; animals; mice; animal tissue; gene expression; animal experiment; animal model; dexamethasone; vascularization; gene transfer; wound healing; gene therapy; blood vessel; adenovirus vector; wound healing impairment; wound closure; strength; marker gene; complementary dna; adenoviridae; gelfoam; dna, complementary; mice, inbred c3h; fascia; vascular endothelial growth factors; endothelial growth factors; surgical sponge; gene transfer, horizontal; male; female; priority journal; article; lymphokines; microcrystalline collagen
Journal Title:	Surgery
Volume:	131
Issue:	2
ISSN:	0039-6060
Publisher:	Elsevier Inc.
Date Published:	2002-02-01
Start Page:	219
End Page:	227
Language:	English
DOI:	10.1067/msy.2002.118709
PUBMED:	11854705
PROVIDER:	scopus
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-0036183667&partnerID=40&md5=c213bc9758db2eb0bbffd1a5bc2bb47e
Notes:	Export Date: 14 November 2014 -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/66320