Mesenchymal Stromal Cells Isolated from Ectopic but Not Eutopic Endometrium Display Pronounced Immunomodulatory Activity In Vitro

Abstract

A comparative analysis of the cell surface markers and immunological properties of cell cultures originating from normal endometrium and endometrioid heterotopias of women with extragenital endometriosis was carried out. Both types of cell cultures expressed surface molecules typical of mesenchymal stromal cells and did not express hematopoietic and epithelial markers. Despite similar phenotype, the mesenchymal stromal cells derived from the two sources had different immunomodulation capacities: the cells of endometrioid heterotopias but not eutopic endometrium could suppress dendritic cell differentiation from monocytes as well as lymphocyte proliferation in allogeneic co-cultures. A comparative multiplex analysis of the secretomes revealed a significant increase in the secretion of pro-inflammatory mediators, including IL6, IFN-γ, and several chemokines associated with inflammation by the stromal cells of ectopic lesions. The results demonstrate that the stromal cells of endometrioid heterotopias display enhanced pro-inflammatory and immunosuppressive activities, which most likely impact the pathogenesis and progression of the disease.

Interferon Signaling in the Endometrium and in Endometriosis

“…These contradictory results may result from the difference between rodent models and human cells. MSCs from ectopic endometrium produce more IFN than MSCs from eutopic endometrium in vitro [ 99 ]. Secretion of indoleamine 2,3-dioxygenase 1 (IDO1) is a biomarker for the immunomodulatory activity of bone marrow-derived MSCs [ 100 ].…”