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 deregulation in processes such as inflammation, angiogenesis, migration, apoptosis, and proliferation. Menstrual bloodderived 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 bloodderived stem cells, exosomes from non-endometriotic MenSCs (NE-MenSCs), both unmodified (Exo) and transfected with miR-4289, were applied as treatments to MenSCs from endometriosis patients (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/βcatenin pathway. Scratch assays and reductions in MMP9 expression suggest decreased migration in the Exo and miRExo 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 reduced notably in the miR and miRExo groups. These findings provide preliminary evidence for the therapeutic potential of MenSCderived exosomes, particularly when loaded with miR-4289, as a novel treatment approach for endometriosis.