Evaluating the Effect of Exosome-Encapsulated miR-4289 on Menstrual Blood-Derived Mesenchymal Stem Cells from Endometriosis Patients.

Endometriosis is a benign yet chronic gynecological disorder characterized by dysregulation of processes such as inflammation, angiogenesis, migration, apoptosis, and proliferation. Menstrual blood-derived endometrial stem cells play a crucial role in the retrograde development and progression of endometriotic lesions. To evaluate the therapeutic potential of exosomes derived from menstrual blood-derived stem cells, exosomes from non-endometriotic MenSCs (NE-MenSCs), both unmodified (Exo) and transfected with miR-4289, were applied as treatments to MenSCs from the endometriosis cell line (E-MenSCs). Publicly available databases were used to identify key genes and signaling pathways implicated in endometriosis, from which miR-4289 was selected as an effective regulatory microRNA. Following treatment, cellular migration was assessed by scratch assays; gene expression was evaluated via real-time PCR; protein levels of ROS, IL-10, and IL-1β were measured by ELISA; and ESR1, CTNNB1, and Ki67 levels were determined by Western blotting. The results indicate that treatments significantly reduced the expression of genes associated with inflammation, proliferation, migration, and the Wnt/β-catenin pathway. Scratch assays and reductions in MMP9 expression suggest decreased migration in the Exo and miR-Exo groups. The expression of CTNNB1, IL-1β, and IL-10 was significantly downregulated in treated groups compared to E-MenSCs. In addition, KRAS and IDO1 expression levels were significantly decreased following treatment, and Ki67 protein levels were notably reduced in the miR and miR-Exo groups. These findings highlight the therapeutic potential of MenSC-derived exosomes loaded with miR-4289 as a promising and novel strategy for treating endometriosis.