Umbilical cord-derived mesenchymal stem cell transplantation in vaginal replacement in vitro and in a rat model

Cell transplantation strategies represent a potential therapeutic approach towards repair of congenital vaginal agenesis. In this study, the efficacy and mechanisms of action of treatment with human umbilical cord-derived mesenchymal stem cells (UC-MSCs) on vaginal regeneration was explored. UC-MSC transplantation alone, small intestinal submucosal (SIS) grafting alone, and a combination of UC-MSC transplantation/SIS grafting were performed with a vaginal defect rat model. Histological analyses of tissue sections were subsequently performed. UC-MSCs promoted the recovery of keratinizing squamous epithelium and papillae to nearly the same levels as in normal tissue. Of the treatments tested, UC-MSC transplantation showed optimal performance in inhibiting collagen deposition and accelerating the synthesis of elastin to maintain tissue elasticity. UC-MSC treatment also increased Cyclin D1, Ki67, and CD31 expression as assessed by immunohistochemistry. We also investigated the effects of UC-MSC secretions on keratinocytes in a co-culture model. UC-MSCs significantly stimulated vaginal tissue repair by promoting vaginal epithelium regeneration via paracrine factors but not by exploiting their keratinocyte differentiation potential. Further, UC-MSCs facilitated epithelial cell viability and promoted cell cycle progression via the AKT/GSK3β/Cyclin D1 pathway. These results indicate that UC-MSC transplantation is a feasible approach for vaginal tissue regeneration.