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 7 days 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.

Long-Term Advantages of Ovarian Reserve Maintenance and Follicle Development Using Adipose Tissue-Derived Stem Cells in Ovarian Tissue Transplantation

“…We thus confirmed their ability to induce angiogenesis within a short interval by differentiating into endothelial-like cells and boosting proangiogenic growth factors in revascularized areas [ 9 , 26 , 27 ]. Having developed such a promising strategy to enhance OTT results [ 28 ], the aim of the present study was to investigate the long-term impact of ASCs on ovarian tissue viability and lifespan in terms of follicle survival, development, and endocrine resumption.…”

The Proliferation and Differentiation of Adipose-Derived Stem Cells in Neovascularization and Angiogenesis

“…ASCs are a significant advance in the improvement of the lifespan and quality of ovarian tissue and their effects should be considered further for clinical application [171]. Further studies of the ovarian tissue cryopreservation and transplantation demonstrated faster and better reoxygenation and revascularization of the graft, which means increased follicle survival and reduced apoptosis [172].…”

Reproductive issues in carriers of germline pathogenic variants in the BRCA1/2 genes: an expert meeting

“…The possibility of in vitro maturation (IVM) of immature oocytes retrieved during ovarian tissue processing is currently being investigated with some promising preliminary results [92], but it is not yet a clinical reality. Similarly, advancements on a fibrin matrix (the "artificial ovary") to harvest ovarian tissue outside the body are currently at a translational research stage [93].…”