Human Ovarian Follicles Xenografted in Immunoisolating Capsules Survive Long Term Implantation in Mice

Female pediatric cancer survivors often develop Premature Ovarian Insufficiency (POI) owing to gonadotoxic effects of anticancer treatments. Here we investigate the use of a cell-based therapy consisting of human ovarian cortex encapsulated in a poly-ethylene glycol (PEG)-based hydrogel that replicates the physiological cyclic and pulsatile hormonal patterns of healthy reproductive-aged women. Human ovarian tissue from four donors was analyzed for follicle density, with averages ranging between 360 and 4414 follicles/mm³. Follicles in the encapsulated and implanted cryopreserved human ovarian tissues survived up to three months, with average follicle densities ranging between 2 and 89 follicles/mm³ at retrieval. We conclude that encapsulation of human ovarian cortex in PEG-based hydrogels did not decrease follicle survival after implantation in mice and was similar to non-encapsulated grafts. Furthermore, this approach offers the means to replace the endocrine function of the ovary tissue in patients with POI.