Lentiviral gene therapy with platelet-derived growth factor B sustains accelerated healing of diabetic wounds over time.

Abstract

The treatment of diabetic wounds is a formidable clinical challenge. In this study, lentiviral vectors carrying the human platelet-derived growth factor B (PDGF-B) gene were used to treated diabetic mouse wounds. Full-thickness 2.0-cm x 2.0-cm excisional wounds were created on the dorsa of genetically diabetic C57BL/KsJ-m+/+Lepr(db) mice. Lentiviral vectors containing the PDGF-B gene were injected into the wound margins and base. Mice were killed at 14-, 21-, and 35-day intervals. Measurement of the residual epithelial gap showed a trend towards increased healing in lentiviral PDGF-treated wounds compared with untreated and saline-treated wounds at all time points. At 21 days, there was significantly increased healing in lentiviral PDGF-treated wounds (0.98+/-0.17 cm) compared with saline-treated wounds (1.22+/-0.30 cm; P<0.05). Immunohistochemistry for CD31 revealed significantly increased neovascularization in lentiviral PDGF-treated wounds compared with untreated and saline-treated wounds at 14 and 21 days (P<0.01). Picrosirius red staining demonstrated thicker and more highly organized collagen fibers in treated wounds compared with untreated and saline-treated wounds. Quantitative analysis of collagen content showed a 3.5-fold and 2.3-fold increase in lentiviral PDGF-treated wounds versus untreated and saline-treated wounds, respectively (P<0.01). Lentiviral gene therapy with PDGF-B can sustain diabetic wound healing over time and may possess promising potential in the clinical setting.

• Authors: Li-Xing Man, Juliet C Park, Michael J Terry, James M Mason, Whitney A Burrell, Fangjun Liu, Brent Y Kimball, Sameer M Moorji, James A Lee, Arnold S Breitbart
• Journal: Annals of plastic surgery (Ann Plast Surg) Vol. 55 Issue 1 Pg. 81-6; discussion 86 (Jul 2005) ISSN: 0148-7043 [Print] United States
• PMID: 15985796 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Proto-Oncogene Proteins c-sis

Topics

• Analysis of Variance
• Animals
• Diabetes Mellitus, Experimental (genetics, physiopathology)
• Genetic Therapy (methods)
• Genetic Vectors
• Humans
• Immunoenzyme Techniques
• Lentivirus (genetics)
• Mice
• Mice, Inbred C57BL
• Proto-Oncogene Proteins c-sis (pharmacology)
• Staining and Labeling
• Wound Healing (genetics)