Background and Objectives: Diabetic wounds are difficult to manage. For cell proliferation, migration, differentiation and regeneration, intracellular Ca2+ equilibrium is crucial. Sarcoplasmic reticulum Ca2+ ATPase2 (SERCA2) has been shown to control Ca2+ level in keratinocytes. Adipose derived mesenchymal stem cells (AdMSCs) are essential for the repair of wounds. The therapeutic effect of SERCA2 gene modified AdMSCs was studied and compared to that of AdMSCs on experimentally induced diabetic wound type 1.
Methods and Results: 42 male rats were classified into: Donation group: three were used for stem cell culture, phenotyping, tagging and SERCA2 preparation. 1st Group І (Control Group): nine rats, 2nd Group (Wounded Group): ten rats were injected with streptozotocin (STZ) intraperitoneal (IP) 50 mg, then rats were exposed to wound induction (1x1cm skin incision). 3rd Group (AdMSCs Therapy): ten rats, injected IP with 1x106 AdMSCs. 4th Group (SERCA2 modified AdMSCs Group): ten rats, injected IP with 1x106 SERCA2 modified AdMSCs. By end of 1st and 3rd weeks, induced diabetic wound surface area was measured. 1st 2nd 3rd and 4th Groups were scarified three weeks after diagnosis of diabetes. Serological, biochemical, phenotypic and quantitative studies were done. In 2nd group, inflammatory, fibrotic and degenerative changes were seen in the wound area and in intact skin. In 3rd and 4th groups these changes were ameliorated, more noticed in 4th group. In the 2nd group, a significant difference was found in wound surface area. Phenotypic and quantitative changes were confirmed by serum glucose, skin Ca2+ concentration and western blot analysis.
Conclusions: SERCA2 gene modified AdMSCs therapy exerted a more pronounced ameliorating effect versus AdMSCs' effect.