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<p>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 <i>miR-4289</i>, 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 <i>miR-4289</i> 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 <i>ROS</i>, <i>IL-10</i>, and <i>IL-1β</i> were measured by ELISA; and <i>ESR</i>1, <i>CTNNB1</i>, and <i>Ki67</i> 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 <i>MMP9</i> expression suggest decreased migration in the Exo and miR-Exo groups. The expression of <i>CTNNB1</i>, <i>IL-1β</i>, and <i>IL-10</i> was significantly downregulated in treated groups compared to E-MenSCs. In addition, <i>KRAS</i> and <i>IDO1</i> expression levels were significantly decreased following treatment, and <i>Ki67</i> protein levels were notably reduced in the miR and miR-Exo groups. These findings highlight the therapeutic potential of MenSC-derived exosomes loaded with <i>miR-4289</i> as a promising and novel strategy for treating endometriosis.</p> Graphical Abstract <p></p>

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

  • 期刊论文

  • 发表日期：

    2025年11月11日

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  • Solmaz Mahmoudi,
  • Azar Sheikholeslami,
  • Nasim Hayati Roodbari,
  • Ehsan Ehsani

摘要

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.

Graphical Abstract