Cyclophilin-a as a key paracrine factor replicating hPVSC therapeutic effects in a chemotherapy-induced ovarian damage model

Chemotherapy-induced premature ovarian insufficiency (POI) causes significant fertility loss. We investigated whether human perivascular stem cells (hPVSC) or their secreted factor, cyclophilin-A (CYP-A), could restore ovarian function in mouse of cyclophosphamide (CP)-induced ovarian damage. Mice subjected to acute or fractionated CP regimens were treated with hPVSC or recombinant CYP-A. We assessed ovarian histology, follicle counts, and in vitro fertilization (IVF) outcomes. While ovary-to-body weight ratios recovered only in the high-dose model, both treatments significantly preserved total follicle counts across all developmental stages in both regimens compared to controls. Although oocyte yields remained comparable across groups, both hPVSCs and CYP-A significantly improved fertilization rates and blastocyst quality in the high-dose model. Crucially, CYP-A independently replicated the therapeutic efficacy of hPVSC transplantation. To our knowledge, this is the first report demonstrating that a single defined paracrine factor can substitute for whole-cell therapy in ovarian failure, offering a robust, cell-free strategy for fertility preservation.