Menstrual blood-derived stromal stem cells from women with and without endometriosis reveal different phenotypic and functional characteristics

Abstract

Retrograde flow of menstrual blood cells during menstruation is considered as the dominant theory for the development of endometriosis. Moreover, current evidence suggests that endometrial-derived stem cells are key players in the pathogenesis of endometriosis. In particular, endometrial stromal stem cells have been suggested to be involved in the pathogenesis of this disease. Here, we aimed to use menstrual blood, as a novel source of endometrial stem cells, to investigate whether stromal stem cells from endometriosis (E-MenSCs) and non-endometriosis (NE-MenSCs) women differed regarding their morphology, CD marker expression pattern, proliferation, invasion and adhesion capacities and their ability to express certain immunomodulatory molecules. E-MenSCs were morphologically different from NE-MenSCs and showed higher expression of CD9, CD10 and CD29. Furthermore, E-MenSCs had higher proliferation and invasion potentials compared with NE-MenSCs. The amount of indoleamine 2,3-dioxygenase-1 (IDO1) and cyclooxygenase-2 (COX-2) in E-MenSCs co-cultured with allogenic peripheral blood mononuclear cells (PBMCs) was shown to be higher both at the gene and protein levels, and higher IDO1 activity was detected in the endometriosis group. However, NE-MenSCs revealed increased concentrations of forkhead transcription factor-3 (FOXP3) when compared with E-MenSCs. Nonetheless, interferon (IFN)-γ, Interleukin (IL)-10 and monocyte chemoattractant protein-1 (MCP-1) levels were higher in the supernatant of E-MenSCs-PBMC co-cultures. Here, we showed that there are inherent differences between E-MenSCs and NE-MenSCs. These findings propose the key role MenSCs could play in the pathogenesis of endometriosis and further support the retrograde and stem cell theories of endometriosis. Hence, considering its renewable and easily available nature, menstrual blood could be viewed as a reliable and inexpensive material for studies addressing the cellular and molecular aspects of endometriosis.

Keywords: IDO1; endometriosis; menstrual blood; stromal stem cells; surface marker expression.