Engineered endothelium provides angiogenic and paracrine stimulus to grafted human ovarian tissue

工程内皮为移植的人类卵巢组织提供血管生成和旁分泌刺激

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作者:Limor Man, Laura Park, Richard Bodine, Michael Ginsberg, Nikica Zaninovic, Omar Alexander Man, Glenn Schattman, Zev Rosenwaks, Daylon James

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.

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