Enhanced Healing Of Diabetic Wounds By Subcutaneous Administration Of Human Umbilical Cord Derived Stem Cells And Their Conditioned Media

Objective:To evaluate if transplantation of umbilical cord derived mesenchymal stem cells and their conditioned media could promote the delayed wound healing in diabetic mice and to investigate the possible mechanisms involved in this process.Methodology:Delayed wound healing animal models were established by making a standard wound on the dorsum of db/db mice. Eighteen db/db mice were divided into three groups with six mice in each: group I, diabetic controls; group II, diabetic mice with subcutaneous injection of umbilical cord derived mesenchymal stem cells; group Ⅲ, diabetic mice with subcutaneous injection of conditioned media of umbilical cord derived mesenchymal stem cells. The rate of wound contraction was measured every alternate day. At the end of two weeks, angiogenesis and the expression of growth factors in wound tissues were evaluated by immunohistochemistry and RT-PCR respectively. Statistical analysis was done by Student’s paired t-test for paired samples and ANOVA for multiple groups and p values of less than0.05were considered significant.Principal Findings:The transplantation of umbilical cord derived mesenchymal stem cells and their conditioned media significantly accelerated wound closure in db/db mice compared PBS treated wounds. Injection of CM could accelerate wound closure, and the enhancement was even better and more rapid than that achieved by UC-MSC transplantation. Significant differences in capillary densities in day-14wounds among the three groups was noted and it was the maximum in CM-treated wounds(n=6; p<0.05). RT-PCR analysis at14days revealed higher levels of VEGF, PDCiF and KGF expression in the CM and UC-MSC-injected wounds compared to the PBS treated wounds and the expression levels of PDGF-p and KGF were higher in CM-treated wounds than in UC-MSC-treated wounds. Conclusions:Both the transplantation of umbilical cord derived mesenchymal stem cells and their conditioned media are beneficial to diabetic wound healing. Conditioned medium has been shown to be therapeutically better than mesenchymal stem cells, at least in the context of diabetic wound healing, suggesting that conditioned medium may be considered as a potential therapeutic option.5figures,7tables,134references...