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Titolo:
Enhanced vascularization of cultured skin substitutes genetically modifiedto overexpress vascular endothelial growth factor
Autore:
Supp, DM; Supp, AP; Bell, SM; Boyce, ST;
Indirizzi:
Shriners Burns Hosp, Shriners Hosp Crippled Children, Res Dept, Cincinnati, OH 45229 USA Shriners Burns Hosp Cincinnati OH USA 45229 ept, Cincinnati, OH 45229 USA Childrens Hosp Res Fdn, Div Mol & Dev Biol, Cincinnati, OH 45229 USA Childrens Hosp Res Fdn Cincinnati OH USA 45229 , Cincinnati, OH 45229 USA
Titolo Testata:
JOURNAL OF INVESTIGATIVE DERMATOLOGY
fascicolo: 1, volume: 114, anno: 2000,
pagine: 5 - 13
SICI:
0022-202X(200001)114:1<5:EVOCSS>2.0.ZU;2-Q
Fonte:
ISI
Lingua:
ENG
Soggetto:
INTRAMUSCULAR GENE-TRANSFER; PERMEABILITY FACTOR; VESSEL DEVELOPMENT; COMPOSITE GRAFTS; TRANSGENIC MICE; WOUND CLOSURE; ATHYMIC MICE; CELLS; EXPRESSION; ANGIOGENESIS;
Keywords:
gene therapy; tissue engineering; wound healing; vascular endothelial growth factor;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
35
Recensione:
Indirizzi per estratti:
Indirizzo: Boyce, ST Shriners Burns Hosp, Shriners Hosp Crippled Children, Res Dept, 3229 Burnet Ave, Cincinnati, OH 45229 USA Shriners Burns Hosp 3229 Burnet Ave Cincinnati OH USA 45229 USA
Citazione:
D.M. Supp et al., "Enhanced vascularization of cultured skin substitutes genetically modifiedto overexpress vascular endothelial growth factor", J INVES DER, 114(1), 2000, pp. 5-13

Abstract

Cultured skin substitutes have been used as adjunctive therapies in the treatment of burns and chronic wounds, but they are limited by lack of a vascular plexus. This deficiency leads to greater time for vascularization compared with native skin autografts and contributes to graft failure. Genetic modification of cultured skin substitutes to enhance vascularization could hypothetically lead to improved wound healing. To address this hypothesis, human keratinocytes were genetically modified by transduction with a replication incompetent retrovirus to overexpress vascular endothelial growth factor, a specific and potent mitogen for endothelial cells. Cultured skin substitutes consisting of collagen-glycosaminoglycan substrates inoculated with human fibroblasts and either vascular endothelial growth factor-modified or control keratinocytes were prepared, and were cultured in vitro for 21 d. Northern blot analysis demonstrated enhanced expression of vascular endothelial growth factor mRNA in genetically modified keratinocytes and in cultured skin substitutes prepared with modified cells. Furthermore, the vascular endothelial growth factor-modified cultured skin substitutes secreted greatly elevated levels of vascular endothelial growth factor protein throughout the entire culture period. The bioactivity of vascular endothelial growth factor protein secreted by the genetically modified cultured skin substitutes was demonstrated using a microvascular endothelial cell growth assay. Vascular endothelial growth factor-modified and control cultured skin substitutes were grafted to full-thickness wounds on athymic mice, and elevatedvascular endothelial growth factor mRNA expression was detected in the modified grafts for at least 2 wk after surgery. Vascular endothelial growth factor-modified grafts exhibited increased numbers of dermal blood vessels and decreased time to vascularization compared with controls. These results indicate that genetic modification of keratinocytes in cultured skin substitutes can lead to increased vascular endothelial growth factor expression, which could prospectively improve vascularization of cultured skin substitutes for wound healing applications.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 27/11/20 alle ore 03:27:48