Translational research aiming to improve survival of ovarian tissue transplants using adipose tissue-derived stem cells.

Abstract

There is now sufficient evidence to support the feasibility and efficacy of ovarian tissue (OT) cryopreservation and transplantation for both fertility preservation and restoration purposes. However, there are still issues to address regarding the grafting procedure itself, since transplanted tissue suffers massive follicle loss in the early post-grafting period. To improve follicle survival after transplantation, our group recently developed a two-step transplantation technique for OT transplantation in a xenografting model using adipose tissue-derived stem cells (ASCs). The aim of this narrative review is to describe and discuss the previously reported findings. ASCs were initially characterized by flow cytometry as positive for CD29, CD44, CD73, CD90, CD105 and CD166 (>95%) and negative for CD34, CD14, CD31, CD45 and Lin1. ASCs were used in a model of xenotransplantation, were they were embedded in a fibrin scaffold and transplanted to the peritoneum of immunodeficient mice. The goal of the first step was to increase levels of partial pressure of oxygen (pO2 ) and revascularization in the peritoneal transplantation site for further OT transplantation. As ASCs showed the ability to differentiate into endothelial-like cells and vessels in our model, OT transplantation was then performed with ASC grafts in a controlled experiment. At 7days post-transplantation, the ASC group showed: (1) significantly higher pO2 levels; (2) significantly greater human and murine CD34-positive endothelial areas; (3) significantly higher primordial follicle survival rates; (4) and significantly lower numbers of apoptotic follicles compared with the control group. Our research model demonstrates that by adding ASCs to a fibrin scaffold before OT transplantation, faster and better graft reoxygenation and revascularization may be obtained, resulting in increased follicle survival and reduced follicle apoptosis.