Therapeutic potential of umbilical cord-derived mesenchymal stem/stromal cells versus their conditioned media on treatment of polycystic ovary In-vivo.

Polycystic ovary syndrome (PCOS) is a common endocrine and reproductive disorder affecting females of reproductive age. This study explored the therapeutic potential of umbilical cord-derived mesenchymal stem cells (UC-derived MSCs) and their conditioned medium (UC-derived MSCs-CM) in a letrozole-induced PCOS rat model (n = 8 per group; four groups: control, PCOS, MSC-treated, and MSC-CM-treated). An additional subset (n = 5 per group) was used for mating studies. Various assessments were carried out, including fertility outcomes, monitoring of the estrous cycle, hormonal profiling (including testosterone, luteinizing hormone [LH], follicle-stimulating hormone [FSH], LH/FSH ratio, progesterone, estrogen, and insulin), insulin resistance index (HOMA-IR), lipid metabolism parameters (cholesterol, triglycerides, low-density lipoprotein [LDL], and high-density lipoprotein [HDL]), oxidative stress biomarkers (glutathione and malondialdehyde [MDA]), and markers of apoptosis (Annexin V/PI and Caspase-3). Histological and immunohistochemical analyses of ovarian and uterine tissues were also completed. Data were analyzed using one-way ANOVA with Tukey's post hoc test for most parameters, the Kruskal-Wallis test with Dunn's post hoc test for non-normally distributed variables, and Fisher's exact test for pregnancy rates. Results are presented as mean ± SD, and significance was set at p < 0.05. Inducing PCOS led to reproductive and metabolic problems, including high androgen levels, increased insulin levels, elevated HOMA-IR, abnormal lipid levels, heightened oxidative stress, increased apoptotic activity, and raised proinflammatory cytokine levels. Both UC-derived MSCs and UC-derived MSCs-CM treatments significantly enhanced these issues by reducing oxidative stress, lowering apoptotic and inflammatory markers, and balancing reproductive hormones. Remarkably, UC-derived MSCs treatment has shown stronger effects, restoring normal estrous cycles, improving ovarian structure, and resulting in positive pregnancy outcomes. These findings suggest that UC-derived MSCs could be a promising cell-based treatment for PCOS and that UC-derived MSCs-CM might be a safe, cell-free alternative with significant therapeutic potential.