The therapeutic potential of exosomes derived from mesenchymal stem cells for premature ovarian failure: A systematic review

This review evaluates mesenchymal stem cell-derived exosomes (MSC-Exos) for treating premature ovarian failure (POF). A comprehensive search was conducted across five databases, including PubMed, Embase, and Web of Science (WoS), yielding 17 English-language studies published between 2016 and 2025. Studies primarily using animal and in vitro models assessed the therapeutic effects and mechanisms of MSC-Exos from diverse sources. MSC-Exos significantly elevated estrogen levels, reduced follicle-stimulating hormone (FSH), increased antral follicle counts, and restored estrous cyclicity. Specifically, BMSC-Exos activated the PI3K/AKT pathway via miRNAs to suppress granulosa cell apoptosis; hUCMSC-Exos mitigated cellular senescence and autophagy; ADSC-Exos promoted follicular development through SMAD and SIRT1/FOXO1; PMSC-Exos attenuated ROS damage by improving mitochondrial function; AFSC-Exos together with MenSC-Exos enhanced oocyte maturation via the P53 pathway. Notably, perinatal exosomes showed 18-32% greater efficacy in functional recovery than adult-tissue counterparts with fewer doses. MSC-Exos present a promising therapeutic strategy for POF by targeting apoptosis, autophagy, angiogenesis, and oxidative stress. Perinatal-derived exosomes offer superior potential due to their non-invasive collection and minimal ethical concerns. Nonetheless, challenges pertaining to heterogeneity, long-term safety, and standardized manufacturing necessitate resolution through multicenter clinical trials to advance clinical applicability..