Lentiviral Gene Therapy With Platelet-Derived Growth Factor B Sustains Accelerated Healing of Diabetic Wounds Over Time

Autor: Juliet C. Park, Michael J. Terry, Sameer M. Moorji, Whitney A. Burrell, James A. Lee, Brent Y. Kimball, Arnold S. Breitbart, Fangjun Liu, Li-Xing Man, James M. Mason
Rok vydání: 2005
Předmět:
Zdroj: Annals of Plastic Surgery. 55:81-86
ISSN: 0148-7043
DOI: 10.1097/01.sap.0000168211.76318.fa
Popis: 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.
Databáze: OpenAIRE