Enhanced Exosomes: A Breakthrough Therapy for Chemotherapy-Induced Premature Ovarian Insufficiency

Abstract

Background Premature ovarian insufficiency (POI) presents a multifaceted challenge with limited treatment options. This study explored the therapeutic potential of exosome-based interventions for chemotherapy-induced POI. Methods With a novel culture system, enhanced exosomes were engineered from umbilical cord mesenchymal stem cells (UC-MSCs), demonstrating superior efficacy compared to naïve exosomes. Results In vitro models revealed the significant impact of enhanced exosomes secretion, which promoted granulosa cell proliferation, mitigated apoptosis, and enhanced ovarian functional markers. The findings in an in vivo chemotherapy-induced POI mouse model underscored the restoration of ovarian morphology, follicle numbers, and fertility in both the naïve and enhanced exosome-treated groups. Notably, the enhanced exosome group demonstrated a heightened pregnancy rate, increased numbers of primary follicles, and a significant reduction in ovarian apoptosis. Safety assessments indicated the feasibility and safety of intravenous exosome administration. MiRNA profiling revealed distinctive cargo in the enhanced exosomes, among which miR-20b-5p played a pivotal role in regulating apoptosis and inflammation; this finding is especially important given that apoptosis is one of the primary complications of chemotherapy-induced POI. Furthermore, cells treated with enhanced amounts of exosomes demonstrated significant overexpression of miR-20b-5p, resulting in decreased PTEN expression and the activation of the PI3K-AKT pathway—a crucial mechanism in mitigating chemotherapy-induced POI. Conclusions This study introduces an innovative exosome-based therapeutic paradigm, accentuating the pivotal role of cargo composition. Further exploration of the identified miRNA profile in enhanced exosomes is warranted for elucidating the underlying mechanisms involved, as this approach could lead to breakthroughs in clinical POI treatment.