Introduction:
Endometriosis as a non-malignant gynecologicaldisease, shows characteristics almost similar to cancer andleads to dysregulation of numerous cellular functions which canincrease the risk of endometrial and breast cancers. Accumulatingevidence has shed light on the importance of endometrialstem cells within the menstrual blood which are involved in theestablishment of endometriotic lesions in a retrograde manner.According to the fact that therapeutic benefits of mesenchymalstem cells are provided through paracrine functions, we usedexosomes from menstrual blood-derived stem cells (MenSCs)to treat endometriotic stem cells which have higher proliferativeand migratory features than MenSCs from healthy women.Methods:
Menstrual blood samples from healthy and endometriosiswomen were collected. Isolated MenSCs by the Ficoll-Paque density-gradient centrifugation were cultured andexosomes were isolated and characterized (Fig. ۱) from non-endometrioticMenSCs (NE-MenSCs) and used to treat endometrioticcells (E-MenSCs). ۷۲ hours after treatment, proliferationand migration were analyzed using Real-Time PCR, immunocytochemistryand scratching assay.Results: Our findings showed that MMP-۲ and MMP-۹, as migratorygenes, were more expressed in E-MenSCs compared toNE-MenSCs (۷.۶ and ۵.۸ times; p<۰.۰۵). Surprisingly, MSCExotreatment could significantly reduce their expression inE-MenSCs (Fig. ۲). Furthermore, scratch assay showed highermigration potential of E-MenSCs than NE-MenSCs, which wassignificantly decreased in E-MenSCs after MSC-Exo treatmentat ۲۴, ۴۸, and ۷۲ h post-scratch (Fig. ۲). Inverted fluorescencemicroscopy images showed lower expression of Ki۶۷ after exosometreatment (Fig. ۳). The expression level of cyclin D۱, asa proliferative marker, had significantly higher expression inE-MenSCs compared to NE-MenSCs, which was significantlydecreased in E-MenSCs after MSC-Exo treatment (Fig. ۴).Conclusion: In this study, we give preliminary evidence for thepotential of MenSCs-Exo for ameliorating endometriosis. Thisstudy suggests that MenSCs-derived exosomes can be consideredas a promising treatment option to improve endometriosiscompared to common and conventional treatments