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

Abstract

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.

Computational drug repurposing effort for identifying novel hits for the treatment of diseases such as endometriosis, uterine fibroids, and prostate cancer

“…The hypothalamic-pituitary-gonadal triad is a specialized structure on sexual characteristics such as the development of sexual characteristics, reproduction, and preservation of sexual characteristics. The stable operation of this triple structure is of great importance in the reproductive activities of the living organism [ 1 – 4 ]. The most important regulator of this mechanism is the gonadotropin-releasing hormone (GnRH), which is secreted by the hypothalamus and has a peptide structure.…”

“…GnRH, especially GnRH-1, has a decapeptide structure. The arrangement and structure of amino acid residues is (pyro) Glu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH 2 [ 4 ]. GnRH peptide initiates reproductive functions by activating the receptor and releasing gonadotropin hormones [ 5 ].…”