A distinct Frequency of Endometrial Stem/Progenitor Cells (EnSCs) in the Ectopic and Eutopic Endometrium of Women with Endometriosis.

Abstract

Endometriosis is a chronic estrogen-dependent disorder characterised by the growth of endometrial-like tissues outside the uterus. Recent data suggest a potential role for endometrial stem/progenitor cells in the development of endometriosis. However, evidence on the frequency of various stem cell populations in ectopic lesions and their paired eutopic counterparts remains limited. Hence, this study assessed the frequencies of endometrial stem cells and their characteristics in eutopic and ectopic endometria of women with endometriosis, and also probed whether these attributes differ in women without endometriosis. We analysed the frequencies of endometrial stem cells and their functional properties, isolated from ectopic lesions and paired eutopic endometrium, in women with endometriosis (n = 72) and women without endometriosis (n = 24). Comparative analysis revealed that the eutopic endometrium had a significantly increased frequency of SUSD2+ eMSCs in women with endometriosis than in those without the disease. Immunophenotypic characterisation of SUSD2+ eMSCs using classical MSC markers (CD73, CD90, CD105, and HLA-ABC) revealed that they retained more than 80% positivity in the eutopic endometrium, whereas variable expression of these markers was observed among ectopic lesions. On functional characterisation, the wound healing assay revealed that eMSCs from deep infiltrating endometriosis have increased migratory capacity compared to control and paired eutopic endometrium. Moreover, a preponderance of eEPCs (N-cadherin+ SSEA-1+ and N-cadherin- SSEA-1+) was observed in the eutopic endometrium of endometriosis. In contrast, a significantly increased frequency of Side Population was observed in ectopic lesions compared to eutopic endometrium. Besides Side Population, ovarian endometrioma exhibited a significantly increased frequency of pericyte eMSCs co-expressing CD146 and CD140b. These findings clearly demonstrated a distinct frequency of endometrial stem/progenitor cells in endometriosis. Collectively, this study underscores the predominance of endometrial stem cells and highlights altered immunophenotypic characteristics and enhanced migration capabilities of ectopic eMSCs, possibly driven by unique cellular microenvironments.