Co-transplantation of Human Ovarian Tissue with Engineered Endothelial Cells: A Cell-based Strategy Combining Accelerated Perfusion with Direct Paracrine Delivery.

TitleCo-transplantation of Human Ovarian Tissue with Engineered Endothelial Cells: A Cell-based Strategy Combining Accelerated Perfusion with Direct Paracrine Delivery.
Publication TypeJournal Article
Year of Publication2018
AuthorsMan L, Park L, Bodine R, Ginsberg M, Zaninovic N, Schattman G, Schwartz RE, Rosenwaks Z, James D
JournalJ Vis Exp
Issue135
Date Published2018 05 16
ISSN1940-087X
KeywordsAnimals, Endothelial Cells, Female, Humans, Mice, Ovary, Paracrine Communication, Tissue Engineering
Abstract

Infertility is a frequent side effect of chemotherapy and/or radiotherapy and for some patients, cryopreservation of oocytes or embryos is not an option. As an alternative, an increasing number of these patients are choosing to cryopreserve ovarian tissue for autograft following recovery and remission. Despite improvements in outcomes among patients undergoing auto-transplantation of cryopreserved ovarian tissue, efficient revascularization of grafted tissue remains a major obstacle. To mitigate ischemia and thus improve outcomes in patients undergoing auto-transplantation, we developed a vascular cell-based strategy for accelerating perfusion of ovarian tissue. We describe a method for co-transplantation of exogenous endothelial cells (ExECs) with cryopreserved ovarian tissue in a mouse xenograft model. We extend this approach to employ ExECs that have been engineered to constitutively express Anti-Mullerian hormone (AMH), thus enabling sustained paracrine signaling input to ovarian grafts. Co-transplantation with ExECs increased follicular volume and improved antral follicle development, and AMH-expressing ExECs promoted retention of quiescent primordial follicles. This combined strategy may be a useful tool for mitigating ischemia and modulating follicular activation in the context of fertility preservation and/or infertility at large.

DOI10.3791/57472
Alternate JournalJ Vis Exp
PubMed ID29863664
PubMed Central IDPMC6101226
Grant ListK08 DK101754 / DK / NIDDK NIH HHS / United States