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

TitleEngineered endothelium provides angiogenic and paracrine stimulus to grafted human ovarian tissue.
Publication TypeJournal Article
Year of Publication2017
AuthorsMan L, Park L, Bodine R, Ginsberg M, Zaninovic N, Man OAlexander, Schattman G, Rosenwaks Z, James D
JournalSci Rep
Volume7
Issue1
Pagination8203
Date Published2017 08 15
ISSN2045-2322
KeywordsAdolescent, 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.

DOI10.1038/s41598-017-08491-z
Alternate JournalSci Rep
PubMed ID28811567
PubMed Central IDPMC5557862
Grant ListUL1 TR002384 / TR / NCATS NIH HHS / United States