Therapeutic potential of super activated platelet lysate (sPL), and mesenchymal stem cells (MSCs) in a rat model with immune premature ovarian failure

OBJECTIVE: Premature ovarian failure (POF) is a complex endocrine disorder that mostly affects women under 40. It is estimated that 4-30 % of POF cases are associated with autoimmunity. The current available treatment options for autoimmune premature ovarian failure (APOF) are limited and often yield unsatisfactory outcomes. Recent studies have demonstrated that stem cell therapy can restore ovarian function and increase quality of life for women affected by POF. METHODS: In this study, a rat model of premature ovarian failure (POF) was established. Superactivated platelet lysate (sPL), mesenchymal stem cells (MSCs), and sPL/MSCs combination therapy were used to treat POF rats. The therapeutic effects were evaluated by detecting key parameters such as estrous cycle, follicle morphology, and hormone secretion, as well as cellular processes including proliferation and apoptosis. RESULT: Our results revealed a notable normalization of the estrous cycle and significant improvements in follicular development after transplantation of sPL, MSCs, and sPL/MSCs. Furthermore, a substantial increase in serum estradiol (E2), progesterone (P4), and anti-Müllerian hormone (AMH) levels was observed after treatment. Gene expression analyses demonstrated an up-regulation of Bcl-2, AMH, and FSHR in the ovaries of APOF rats following transplantation with sPL, MSCs, and sPL/MSCs. Remarkably, the combined treatment of sPL/MSCs for 4 weeks exhibited the most significant effects, with comparable results across all treatment groups after 8 weeks. These findings collectively indicate the positive therapeutic impact of sPL, MSCs, and their combination in addressing autoimmune-induced premature ovarian failure. In addition, these findings provide valuable insights for potential clinical applications in treating autoimmune-induced premature ovarian failure. CONCLUSION: Our research shows that sPL, MSCs, and sPL/MSCs all improve the physiological status of ovaries with autoimmune POF, regulate hormone levels and gene expression, increase the number of follicles, and regulate cell apoptosis and growth. In particular, after 4 weeks of combined transplantation therapy with sPL and MSCs, the synergistic therapeutic effect produced can more rapidly improve autoimmune POF caused by anti-zona pellucida antibodies, which is superior to other treatment groups.