Human endometrial mucosa is a dynamically remodeling tissue, undergoing cyclical morphologic and functional changes in response to fluctuating sex steroid hormones each menstrual cycle during a woman's reproductive life. Postmenopausal endometrium responds similarly to exogenous estrogen. Cyclical endometrial regeneration also occurs in nonmenstruating rodents, although to a lesser extent. The recent identification of rare populations of endogenous epithelial progenitor cells, mesenchymal stem/stromal cells (MSCs), the side population (SP) cells, and label-retaining cells (LRCs) suggests these stem/progenitor cell populations may play a key role in endometrial regeneration during menstrual and estrus cycles. This review summarizes the identification of epithelial progenitors, MSC, SP, and LRC, and discusses their contribution to endometrial tissue regeneration, maintaining tissue homeostasis, decidualization, and placentation. Markers for human endometrial MSC have been identified, revealing their perivascular location in both the functionalis and basalis layers. These markers also allow their purification from biopsy tissue and menstrual blood. These findings have advanced our understanding of normal endometrial physiology and will provide new insight into endometrial proliferative disorders (endometriosis, endometrial cancer). The ability to prospectively isolate endometrial MSC will enable their utilization in cell-based therapies for reproductive tract pathologies.
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