Abstract
Despite major advances in tissue cryopreservation and auto-transplantation, reperfusion ischemia and hypoxia have been reported as major obstacles to successful recovery of the follicular pool within grafted ovarian tissue. We demonstrate a benefit to follicular survival and function in human ovarian tissue that is co-transplanted with exogenous endothelial cells (ExEC). ExECs were capable of forming functionally perfused vessels at the host/graft interface and increased both viability and follicular volume in ExEC-assisted grafts with resumption of antral follicle development in long-term grafts. ExECs that were engineered to constitutively express anti-mullerian hormone (AMH) induced a greater proportion of quiescent primordial follicles than control ExECs, indicating suppression of premature mobilization that has been noted in the context of ovarian tissue transplantation. These findings present a cell-based strategy that combines accelerated perfusion with direct paracrine delivery of a bioactive payload to transplanted ovarian tissue.
Highlights
For patients diagnosed with cancer, survival rates are improving[1], drawing increased attention to options for preserving reproductive options following remission
These phenotypes suggest that Anti-mullerian hormone (AMH) suppresses mobilization of primordial follicles, subsequent work in sheep concluded that AMH does not influence mobilization, but instead regulates the rate of early follicle progression[23]
Due in large part to assisted reproductive technologies, cryopreservation protocols have significantly improved, yet a large degree of grafted tissue is still lost following in vivo transplant due to ischemia[14, 25,26,27]
Summary
Due in large part to assisted reproductive technologies, cryopreservation protocols have significantly improved, yet a large degree of grafted tissue is still lost following in vivo transplant due to ischemia[14, 25,26,27]. After two weeks GFP-labeled ExECs formed functionally perfused vessels at the interface of graft and host tissue, thereby restoring blood flow to tissue (Fig. 2b and Supplementary Figure 1b). Quantification of follicular survival at 2 weeks following transplant demonstrated a significant benefit to relative follicle count in ExEC-assisted grafts (Fig. 2c and d and Table 1), with a majority of experiments favoring ExECs derived from either mouse (heart ECs) or human (hUVEC). Two weeks after co-transplantation, vessels derived from AMH-ExECs were observed at the host-graft interface and immunostaining revealed abundant AMH protein in the lumen of these vessels (Fig. 4d); co-transplantation with AMH-ExECs resulted in an approximately two-fold increase in the percentage of primordial follicles relative to control ExECs, while the percentage of primary follicles was decreased (Fig. 4e and g). Ewing’s sarcoma Hodgkin’s stage IV Beta Thalassemia Thalassemia Major Cancer Hodgkin’s Lymphoma
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
