ISSN:
1524-475X
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Diabetic wounds are characterized by disruption of the normal wound repair responses, particularly at the inflammatory and proliferative stages. Inadequate levels of growth factors, such as platelet-derived growth factor (PDGF), play a significant role in the impaired healing of these wounds. PDGF is a potent mitogen and chemotactic agent, and is released from platelet alpha-granules during the acute inflammatory phase of wound healing. It has been shown to promote the deposition of collagen and granulation tissue, and improves healing in diabetic animals. Although previous studies have shown some success with topically applied PDGF, results in clinical practice have been moderate. In this study, we investigated whether gene therapy with lentiviral vectors carrying the gene for PDGF can improve wound healing in an animal model. Full thickness 2 cm × 2 cm dermal wounds were created on the dorsae of genetically diabetic db/db mice. Lentiviral vectors containing the human PDGF-beta gene (lenti-PDGF) were injected into the wound margins and along the wound base. Control experiments were performed using phosphate-buffered saline (PBS) injections. Mice were sacrificed after 21 days, and wound tissues were harvested for histological analyses. Lenti-PDGF-treated animals demonstrated significantly smaller residual epithelial gaps compared to PBS controls (0.77 +/− 0.07 cm vs. 1.22 +/− 0.30 cm; P 〈 0.001), as well as a greater degree of wound closure (85 +/− 3% vs. 57 +/− 22%; P 〈 0.05). Lentiviral gene therapy with PDGF is effective in promoting wound healing in genetically diabetic animals, and warrants further investigation.Supported by a grant from the American Diabetes Association
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1111/j.1067-1927.2005.130216ba.x
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