Title | Engineered endothelium provides angiogenic and paracrine stimulus to grafted human ovarian tissue. |
Publication Type | Journal Article |
Year of Publication | 2017 |
Authors | Man L, Park L, Bodine R, Ginsberg M, Zaninovic N, Man OAlexander, Schattman G, Rosenwaks Z, James D |
Journal | Sci Rep |
Volume | 7 |
Issue | 1 |
Pagination | 8203 |
Date Published | 2017 08 15 |
ISSN | 2045-2322 |
Keywords | Adolescent, Animals, Biomarkers, Child, Cryopreservation, Endothelial Cells, Endothelium, Female, Fertility Preservation, Fluorescent Antibody Technique, Graft Survival, Humans, Mice, Neovascularization, Physiologic, Ovary, Paracrine Communication, Tissue Engineering, Transplants, Young Adult |
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. |
DOI | 10.1038/s41598-017-08491-z |
Alternate Journal | Sci Rep |
PubMed ID | 28811567 |
PubMed Central ID | PMC5557862 |
Grant List | UL1 TR002384 / TR / NCATS NIH HHS / United States |