Endometrial stem/progenitor cells and their role in the pathogenesis of endometriosis

Human endometrium regenerates on a cyclical basis each month, likely mediated by endometrial stem/progenitor cells. Several types of stem/progenitor cells have been identified: CD140b⁺CD146⁺ or SUSD2⁺ endometrial mesenchymal stem cells (eMSCs), N-cadherin⁺ endometrial epithelial progenitor cells (eEPs), and side population (SP) cells, a heterogeneous population predominantly comprising endothelial cells. eMSCs reside in a perivascular niche and likely mediate angiogenesis and stromal regeneration. Human eEPs are located in the bases of glands in the basalis and are likely more primitive than SSEA-1⁺ basalis epithelial cells. Endometrial stem/progenitor cells may contribute to the pathogenesis of endometriosis by their retrograde shedding into the pelvic cavity, either after menarche or as a result of neonatal uterine bleeding. eMSCs may have a role in the generation of progesterone-resistant phenotype of endometrial stromal fibroblasts (eSFs) in endometriosis. In future clinical practice, endometrial stem/progenitor cells may be used to establish diagnosis of endometriosis or as therapeutic targets.