Exosomes derived from different sources of mesenchymal stem cells attenuate cisplatin-induced ovarian toxicity.

Premature ovarian insufficiency (POI) poses significant challenges to reproductive health due to follicular depletion and hormonal dysregulation. Despite advances in stem cell therapy, clinical translation remains hindered by donor variability and ethical constraints. This study evaluates the therapeutic potential of exosomes derived from induced pluripotent stem cell-derived mesenchymal stem cells (iPSCMSC-exo) versus umbilical cord-derived MSC exosomes (hUCMSC-exo) for POI intervention. In vitro, both exosome types enhanced migration and tube formation of human umbilical vein endothelial cells (HUVECs), while iPSCMSC-exo additionally promoted proliferation. iPSCMSC-exo attenuated cisplatin-induced granulosa cell apoptosis, while both types suppressed p21-mediated cell cycle arrest. In the cisplatin-induced POI mouse model, exosome treatment effectively restored Follicle-stimulating hormone (FSH) levels. However, the therapeutic efficacy of exosomes in restoring anti-Müllerian hormone (AMH) levels and follicle counts was limited, as confirmed by synchrotron radiation microtomography revealing persistent structural depletion. Notably, iPSCMSC-exo demonstrated functional outcomes similar to hUCMSC-exo. The autologous origin and scalable production of iPSCMSCs address donor heterogeneity and supply limitations inherent to traditional MSC sources. Further optimization of targeted delivery systems is warranted to overcome biodistribution challenges and enhance structural regeneration.