Local Administration of pCMV-VEGF165 Plasmid Encoding VEGF Stimulates Tissue Regeneration after Cold Injury in Rats

INTRODUCTION. Frostbite is a common cold injury that is associated with high rates of disability and requires long and difficult treatment. A vascular endothelial growth factor (VEGF)-encoding pCMV-VEGF165 plasmid-based gene therapy product designed for therapeutic angiogenesis may be a promising tool to promote microcirculation recovery and accelerate lesion healing in local cold injury. This hypothesis needs to be tested in an experimental animal study. AIM. This study aimed to evaluate the efficacy of the pCMV-VEGF165 plasmid gene therapy product for the management of cold injury of a limb in rats. MATERIALS AND METHODS. The study included 42 mature female outbred white laboratory rats. A third to fourth-degree local cold injury was experimentally induced on the dorsal surface of the left hind paw by applying a neodymium magnet frozen in liquid nitrogen. The animals received periwound injections of the test product (super-coiled circular double-stranded plasmid deoxyribonucleic acid at a dose of 60 μg) and placebo (water for injections) on days 2 and 7 after frostbite modelling. The authors evaluated the general condition of the animals, the condition of the damaged paw, the wound area, the healing rate, the body mass, and, after planned euthanasia, the mass of the hind paws. RESULTS. Starting from day 7, the rats treated with the test product showed significantly faster tissue regeneration at the site of cold injury than the control animals. The mean wound surface area reduction in the test animals amounted to 47.36% [25.55; 55.45], whereas that in the control animals was 28.95±18.55% (p<0.05). On day 10, the test group still had a significantly higher tissue regeneration rate than the control group (58.70±15.35% vs 42.01±17.41%, respectively, p<0.05). Later, there was no statistically significant difference in the wound surface healing rates between the groups, which could probably be attributed to the nature of wound healing in the experimental model since rodent wounds heal predominantly by contraction. CONCLUSIONS. The pCMV-VEGF165 plasmid gene therapy product injected in the periwound area at a dose of 60 μg on days 2 and 7 after cold injury simulation in rats reduces damage, accelerates tissue regeneration under the scab, and expedites scarring.