Lentiviral Gene Transfer of SDF-1α to Wounds Improves Diabetic Wound Healing

BackgroundChronic wounds continue to be a major clinical problem and novel therapeutic approaches are needed. We have previously demonstrated that treatment of diabetic mouse wounds with local application of stromal progenitor cells results in improved healing and increased production of stromal-derived growth factor-1α (SDF-1α). We hypothesized that lentiviral-mediated increased production of SDF-1α in the wound environment could also improve diabetic wound healing.Materials and methodsFull-thickness excisional wounds were created in Db−/Db− mice and immediately treated with 106, 108, or 109 plaque-forming units of a lentiviral construct containing GFP-SDF-1α or GFP alone. At 7 and 14 days post wounding, wounds were harvested for histological and molecular analysis.ResultsAt 7 days, Db−/Db− wounds treated with lenti GFP-SDF-1α exhibited a decrease in wound surface area for all doses tested. Morphologically, SDF-treated wounds were more cellular with increased granulation tissue volume compared to controls (P < 0.05). GFP expression was maintained in treated tissue at 7 days post wounding, but little expression was observed at 14 days. While we did not observe a difference in the gross wound surface area at 14 days, histological analysis revealed that SDF-treated wounds were fully epithelialized (n = 6) compared to only one of six controls.ConclusionsLentiviral-mediated overproduction of SDF-1α is sufficient to correct the pathophysiologic abnormalities in diabetic wound healing resulting in complete epithelialization at 2 weeks. SDF-1α-mediated improvement in diabetic wound healing has significant implications for the development of novel therapeutic strategies to facilitate wound closure which target progenitor cell mobilization and recruitment.