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.

CD10 expression identifies a subset of human perivascular progenitor cells with high proliferation and calcification potentials

“…Maguer‐Satta et al showed that a gradient of peptides generated by CD10 enzyme cleavage is involved, with β1‐integrins, in maintaining mammary stem cells and regulating their conversion to luminal progenitors . CD10 expression by stem cells in the bone marrow, adipose tissue, umbilical cord, hair follicle, and endometrium has been reported . CD10 has also been described as a cancer stem cell marker and its expression associated with metastasis and poor survival .…”

Endometriosis-associated changes in serum levels of interferons and chemokines

“…At the same time, its role in endometriosis is not completely understood. Some authors have described increased IFN-γ mRNA expression in endometriosis compared to eutopic endometrium (12). It is known that IFN-γ inhibits the proliferation of human endometrial epithelium (14), but the resistance of endometriotic cells to IFN-γ-induced cell growth inhibition and apoptosis has been found to be a possible mechanism in endometriosis pathogenesis, and, at the same time, it seems that IFN-γ peritoneal fluid (PF) levels could be suppressed in endometriosis patients (15).…”

“…Elevated levels of MCP-1 in peritoneal fluid and endometrial glands of endometriosis patients have been recently reported (12). Thus, a higher concentration of MCP-1 might be partly responsible for higher IFN-γ production by monocytes and macrophages.…”

Direct Cell–Cell Interactions in the Endometrium and in Endometrial Pathophysiology

“…Thus, an adequate decidualization process is indispensable for successful embryo implantation and development [82]. During this process, the endometrial stromal cells undergo phenotypic changes reminiscent of mesenchymal-epithelial transition leading to epitheloid cells [83,84,85], accompanied by changes in expression and localization of numerous cell–cell contact proteins.…”