Therapeutic potential of adipose-derived mesenchymal stem/stromal cells conditioned medium versus adipose-derived mesenchymal stem/stromal cells on treatment of polycystic ovary In-vivo.

Polycystic ovary syndrome (PCOS) is a prevalent endocrine and metabolic disorder characterized by ovulatory dysfunction and insulin resistance. Adipose tissue-derived Mesenchymal stem/stromal cell (Ad-derived MSCs)-based therapies have shown promising regenerative effects in PCOS models. However, most cell-free therapeutic investigations have primarily focused on MSC-derived exosomes, whereas the therapeutic potential of the complete conditioned medium (CM), which contains a broader spectrum of secreted bioactive factors, remains underexplored. Therefore, this study aimed to compare the therapeutic efficacy of Ad-derived MSCs and their CM in a letrozole-induced PCOS female rat (four groups: control, PCOS, Ad-derived MSCs-treated, and Ad-derived MSCs-CM-treated). Hormonal profiling, reproductive performance, and estrous cyclicity were monitored. Metabolic parameters comprised the insulin resistance index (HOMA-IR) and lipid profile markers. Glutathione and malondialdehyde as oxidative stress biomarkers, Annexin V/PI and Caspase-3 as apoptotic markers, and inflammatory mediators were evaluated alongside histological and immunohistochemical examination of ovarian and uterine tissues. PCOS induction produced endocrine imbalance, insulin resistance, dyslipidemia, oxidative stress, and increased apoptosis with marked ovarian and uterine structural alterations. Both Ad-derived MSCs and CM significantly improved these abnormalities; however, Ad-derived MSCs therapy produced more pronounced effects, restoring estrous cyclicity and fertility outcomes. Nevertheless, Ad-derived MSCs-CM demonstrated substantial therapeutic efficacy, highlighting Ad-derived MSCs-CM as a promising and potentially safer cell-free therapeutic strategy for PCOS.