Antibody Neutralization of Vascular Endothelial Growth Factor Inhibits Wound Granulation Tissue Formation

Howdieshell, Thomas R.; Callaway, Dianne; Webb, Whitney; Gaines, Michael D.; Procter, Charles D.; Sathyanarayana,; Pollock, Jennifer S.; Brock, Tommy L.; McNeil, Paul L.

doi:10.1006/jsre.2001.6089

Cited by 168 publications

(105 citation statements)

References 25 publications

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“…Elevated VEGF mRNA levels were found in keratinocytes at the wound edges and in keratinocytes that migrate to cover the wound surface [36]. Besides, antibody neutralization of this cytokine was shown to inhibit formation of wound granulation tissue [37].…”

Section: Discussionmentioning

confidence: 99%

Adeno-associated viral vector-mediated human vascular endothelial growth factor gene transfer stimulates angiogenesis and wound healing in the genetically diabetic mouse

et al. 2003

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Aims/hypothesis. We studied the gene therapy efficacy of diabetes-associated wound healing disorder with an adeno-associated virus (AAV) vector expressing the 165-amino acid isoform of human vascular endothelial growth factor-A (VEGF-A) by using an incisional skin-wound model produced on the back of female diabetic C57BL/KsJ db+/db+ mice and their normal littermates (db+/+m). Methods. Animals were randomized to receive intradermally into the wound edges either rAAV-LacZ (a control gene), or rAAV-VEGF165. Animals were killed on different days (7 and 14 days after skin injury) and wounded skin tissues were used for gene marker studies, histological evaluation and immunohistochemistry, and wound breaking strength analysis. Furthermore we studied the VEGF mature protein in the wounds. Results. We found that AAV vectors are highly efficient for gene transfer to the mouse skin, displaying an exquisite tropism for the panniculus carnosus by using the beta-galactosidase activity assay. We confirmed the increased expression of the angiogenic factor at day 7 by measuring the wound content of the mature protein. Delivery of VEGF165 to incisional skin wounds of diabetic mice resulted in a remarkable induction of new vessel formation with consequent improvement in the wound healing process. The rAAV-VEGF165 gene improved wound healing in diabetic mice through the stimulation of angiogenesis, reepithelization, synthesis and maturation of extracellular matrix. Moreover the recombinant AAV encoding the human VEGF165 increased the breaking strenght of the wound and enhanced the wound content of VEGF. Conclusion/interpretation. Our study suggests that VEGF gene transfer might represent a new approach to treat wound healing disorders associated with diabetes. [Diabetologia (2003) 46:546-555]

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Section: Discussionmentioning

confidence: 99%

Adeno-associated viral vector-mediated human vascular endothelial growth factor gene transfer stimulates angiogenesis and wound healing in the genetically diabetic mouse

et al. 2003

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“…Moreover, antibody neutralization of this cytokine was demonstrated to inhibit formation of wound granulation tissue. 39 From the above considerations, it follows that local treatment of wounds with VEGF protein or through VEGF gene transfer might represent an important tool to promote efficient wound repair, especially in conditions in which the physiological healing process is impaired, such as in diabetes. 40 As far as treatment with the VEGF protein is concerned, animal experiments and clinical trials have indicated that large, often repeated doses of growth factor are required to attain clinical benefit, suggesting that exogenous presentation can lead to clearance, sequestration 41 or destruction 42 of the factor.…”

Section: Discussionmentioning

confidence: 99%

Recombinant AAV vector encoding human VEGF165 enhances wound healing

et al. 2002

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“…Preclinical studies have shown that inhibition of angiogenesis may impair wound healing (Howdieshell et al, 2001). In clinical trials/observational studies wound healing complication is reported to occur in 0.3-5.6% of patients receiving chemotherapy and Bv (Van Custsem et al, 2007a;Hochster et al, 2006;Kozloff et al, 2006).…”

Section: Surgery and Antibody Therapymentioning

confidence: 99%