A bioengineered in situ ovary (ISO) supports follicle engraftment and live-births post-chemotherapy

作者：Michael J. Buckenmeyer, Meena Sukhwani, Aimon Iftikhar, Alexis L. Nolfi, Ziyu Xian, Srujan Dadi, Zachary W. Case, Sarah Steimer, A. D’Amore, Kyle E. Orwig, Bryan N. Brown · 发表于：Journal of Tissue Engineering · 年份：2023 · DOI：10.1177/20417314231197282 · 被引用次数：16 · 研究领域：Reproductive Biology and Fertility、Tissue Engineering and Regenerative Medicine、Renal and related cancers

Female cancer patients who have undergone chemotherapy have an elevated risk of developing ovarian dysfunction and failure. Experimental approaches to treat iatrogenic infertility are evolving rapidly; however, challenges and risks remain that hinder clinical translation. Biomaterials have improved in vitro follicle maturation and in vivo transplantation in mice, but there has only been marginal success for early-stage human follicles. Here, we developed methods to obtain an ovarian-specific extracellular matrix hydrogel to facilitate follicle delivery and establish an in situ ovary (ISO), which offers a permissive environment to enhance follicle survival. We demonstrate sustainable follicle engraftment, natural pregnancy, and the birth of healthy pups after intraovarian microinjection of isolated exogenous follicles into chemotherapy-treated (CTx) mice. Our results confirm that hydrogel-based follicle microinjection could offer a minimally invasive delivery platform to enhance follicle integration for patients post-chemotherapy.