Polycystic ovarian syndrome (PCOS) is a ubiquitous hormonal disorder and induces female infertility and heterogeneous syndromes, for which there is still no effective treatment. Thanks to the properties of immunomodulatory and endocrine regulation, mesenchymal stem cells (MSCs) have been widely used in various disease types. There were few reports for MSCs injected to ovaries due to the size limitation and complicated vascular network. Here, we develop one simple and efficient approach to deliver and stabilize MSCs in the outside of the ovary without blood leaking through the fibrin gelation, which also possesses excellent biocompatibility to support MSC survival. Notably, the transplantation of MSCs, encapsulated in fibrin hydrogel, could rescue ovarian function more efficiently compared to only MSC control in terms of elevated estradiol (E2) and progesterone (P) levels, diminished gonadotropins (LH/FSH), testosterone (T), and transforming growth factor-β1 (TGF-β1) levels, regular estrous cycles, enhanced number of granulosa cells, and reduced number of immature cystic follicles. The size and weight of the ovary increased for MSCs both within and without fibrin in PCOS rat models in two weeks. Moreover, we have shown the versatility of fibrin hydrogel as a cell-compatible platform for advanced stem cell translation, including identifying novel mechanisms of cell survival support, tissue development, and regenerative medicine.
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