067 Electroporation‐Enhanced Gene Therapy with KGF‐1 Corrects Healing Impairment in Older Diabetic Mice

  Diabetes is known to impair wound healing. We assessed the effect of aging on this impairment and further explored the possibility of repairing age‐dependant impairment by replenishing levels of the growth factor KGF‐1 using our system of electroporation enhanced gene therapy. Methods:  Female BKS.Cg‐ m +/+ Lepr db /J mice (diabetic) were obtained from the Jackson Laboratory (Bar Harbor, ME). Mice at time of study were 7, 27, and 84 weeks, respectively. Two wounds were created using a 5 mm punch biopsy. Plasmid DNA encoding KGF‐1 was injected at 40 μg / wound. Electroporation was carried out with six square wave pulses, at 1800 volts for 100 μs; with aninterval of 125 ms. Wounds were assessed planometrically over a 14‐day period. Results:  We found that wound healing is severely impaired in older, but not young diabetic mice (7‐week‐old mice displayed a threefold smaller wound area than 84‐week‐old mice on day 9). Glucose levels were similar in old and young groups ruling out differences in intensity of the metabolic derangement to explain this disparity (old: 334 +/− 41 mg/dl vs. young: 290 +/− 33 mg/dl). Treatment with KGF‐1 gene therapy increased wound closure in aged mice 5.9‐fold as compared to untreated aged mice 5 days after wounding (treated: 3724 +/− 631 vs. untreated: 632 +/− 517, P = 0.002). Aged KGF‐1 gene therapy‐treated mice closed wounds 10‐fold faster than treated young mice 5 days after wounding (old: 3724: +/− 631 vs. young 358 +/− 871, P = 0.004). Conclusions:  We conclude that progressive damage to the tissues capability to heal occurs in individuals with diabetes. Treatment with KGF‐1 gene therapy is more effective in aged mice than young mice. With an increasing geriatric diabetic population, gene therapy to replenish growth factors may be worth exploring.