Hematogenous Dissemination of Mesenchymal Stem Cells from Endometriosis

Fei Li, Myles H. Alderman, Aya Tal, Ramanaiah Mamillapalli, Alexis Coolidge, Demetra Hufnagel, Zhihao Wang, Elham Neisani, Stephanie Gidicsin, Graciela Krikun, Hugh S Taylor
Stem cells (Dayton, Ohio) · 2018 · vol. 36(6) , pp. 881–890 · doi:10.1002/stem.2804 · PMID:29450941 · PMC5992028 · W2789507794
article OA: bronze CC0 ⤵ 42 in-corpus citations
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⚙ AI-generated summary by claude@2026-06, 2026-06-08 ⓘ

This study found that stem cells from endometriosis lesions can enter the bloodstream, expressing CXCR4 and MSC markers, potentially disseminating the disease to distant sites like the lungs.

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Abstract

Endometriosis is ectopic growth of endometrial tissue traditionally thought to arise through retrograde menstruation. We aimed to determine if cells derived from endometriosis could enter vascular circulation and lead to hematogenous dissemination. Experimental endometriosis was established by transplanting endometrial tissue from DsRed+ mice into the peritoneal cavity of DsRed- mice. Using flow cytometry, we identified DsRed+ cells in blood of animals with endometriosis. The circulating donor cells expressed CXCR4 and mesenchymal stem cell (MSC) biomarkers, but not hematopoietic stem cell markers. Nearly all the circulating endometrial stem cells originated from endometriosis rather than from the uterus. Cells expressing DsRed, CXCR4, and MSCs markers were identified in the peritoneal wall and surrounding vessels of recipient mice, contributing to both endometriosis and angiogenesis. Cells originating in endometriosis lesions migrated and implanted in lung tissue and displayed makers of differentiation, indicating retained multipotency. In vitro these cells demonstrated multipotency and were able to differentiate into adipogenic, osteogenic, and chondrogenic lineages. Endometriosis lesions also expressed high levels of CXCL12, the CXCR4 receptor ligand. Serum CXCL12 levels were greater than in sham control mice. In humans with endometriosis, serum CXCL12 levels were significantly higher than controls, suggesting that the CXCL12/CXCR4 axis is operational in women with spontaneous endometriosis as well. Stem cells, rather than differentiated cells from endometriosis, enter the circulation in response to CXCL12. We identify an endometriosis-derived stem cell population, a potential mechanism of dissemination of this disease and a potential target for treatment of endometriosis. Stem Cells 2018;36:881-890.

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Condition tags

endometriosis

MeSH descriptors

Endometriosis Mesenchymal Stem Cells Adult Animals Cell Differentiation Disease Models, Animal Endometriosis Endometriosis Female Humans Mesenchymal Stem Cells Mice Middle Aged Signal Transduction Young Adult

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