子宫内膜异位症作为一种非恶性妇科疾病，会导致细胞凋亡、血管生成、迁移、增殖和炎症等多种细胞功能的紊乱。越来越多的证据揭示了月经血中内膜干细胞在反行方式下参与了内膜异位症病变的形成和进展的重要性。根据间充质干细胞通过旁分泌功能提供的治疗益处，我们使用月经血源干细胞（MenSCs）释放的外泌体来治疗内膜异位干细胞，以抑制病变的形成倾向。收集了健康和内膜异位症患者的月经血样本。通过浓度梯度离心法分离出MenSCs，并进行了流式细胞术鉴定。从健康的MenSCs（NE-MenSCs）中分离出的外泌体用于治疗内膜异位细胞（E-MenSCs）。治疗后的72小时，通过实时聚合酶链反应、酶联免疫吸附实验、免疫细胞化学、Annexin V/PI和划痕实验分析了包括炎症、增殖、凋亡、迁移和血管生成在内的不同机制和通路。外泌体治疗显著降低了在内膜异位症中异常表达的与炎症、增殖、迁移和血管生成相关的标志物的表达水平。此外，治疗后诱导了内膜异位细胞的凋亡，这在基因和蛋白水平上进行了评估。在本研究中，我们为MenSCs-Exo在改善内膜异位症中的潜力提供了初步证据。根据我们的结果，我们建议在相关临床试验之后，MenSCs来源的外泌体可以被认为是与常规治疗相比，改善内膜异位症的更好治疗选择，并展示其在内膜异位症修复中的潜力作为无细胞产品。©2023生殖生物学协会和波兰科学院奥尔什丁动物繁殖与食品研究所。Elsevier B.V.保留所有权利。

Endometriosis as a non-malignant gynecological disease leads to dysregulation of numerous cellular functions including apoptosis, angiogenesis, migration, proliferation, and inflammation. Accumulating evidence has shed light on the importance of endometrial stem cells within the menstrual blood which are involved in the establishment and progression of endometriotic lesions in a retrograde manner. According to the fact that the therapeutic benefits of mesenchymal stem cells are provided through paracrine functions, we used exosomes from menstrual blood-derived stem cells (MenSCs) for treating endometriotic stem cells to inhibit their lesion formation tendency. Menstrual blood samples from healthy and endometriosis women were collected. Isolated MenSCs by the density-gradient centrifugation method were characterized by flow cytometry. Secreted exosomes were isolated from healthy MenSCs (NE-MenSCs) and used to treat endometriotic cells (E-MenSCs). 72 h after treatment, different mechanisms and pathways including inflammation, proliferation, apoptosis, migration, and angiogenesis were analyzed using Real-Time PCR, ELISA, immunocytochemistry, annexin V/PI, and scratching assay. Exosome treatment significantly reduce the expression level of markers related to inflammation, proliferation, migration, and angiogenesis in E-MenSCs which are aberrantly expressed in endometriosis. Moreover, apoptosis was induced in E-MenSCs after treatment which was evaluated in both gene and protein levels. In this study, we give preliminary evidence for the potential of MenSCs-Exo in ameliorating endometriosis. Regarding our results, we suggest that after relevant clinical trial, MenSCs-derived exosomes can be considered as a better treatment option to improve endometriosis compared to common and conventional treatments and show their potential as a cell-free product in endometriosis repair.Copyright © 2023 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier B.V. All rights reserved.