Stem Cells in Endometrial Physiology

Abstract

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.

Pathogenesis of deep endometriosis

“…Some of these mesenchymal/ mesothelial cells of the peritoneal cavity (48), of the mesothelial repair after surgery (126) and in endometrium and endometriosis (127)(128)(129)(130)(131) are directly derived from bone marrow. Endometriosis could develop from stem cells in the endometrium (132,133) or in the peritoneal cavity (29,(134)(135)(136)(137)(138)(139)(140)(141)(142)(143)(144), possibly induced by genetic changes (60). Recently a specific cell in the endometrium called pale cell (145,146), because of their appearance, was speculated to be involved in endometriosis and adenomyosis development.…”

Stem Cells in Endometrium and Regeneration

“…Epithelial progenitor cells in endometrial unicellular suspensions obtained from hysterectomy tissue to allow testing of basal glands; is clonogenic cells [17]. Identification of epithelial progenitor markers will provide an opportunity to investigate its role, endometrial regeneration in normal cycling endometrium, and gynecological diseases associated with abnormal epithelial proliferation such as endometriosis, endometrial cancer and adenomyosis [3]. The monthly regeneration of the human endometrium, it is almost completely resected after the parturition and in postmenopausal women taking estrogen-based hormone replacement therapy [6].…”

“…The heterogeneity and weak clonogenicity making single cell culture impractical restrict the researchs of the endometrial SP. However, much proof suggests that endometrial stem/progenitor cells are enriched in the SP fraction [20,3]. Although many studies have been achieved on endometrial cells derived from bone marrow, most have not identified the type of bone marrow cells that contribute to the endometrium.…”

“…The regeneration of the human endometrial mucosa, a dynamic tissue, is subjected to periodical functional morphologic changes under the influence of sex hormones that change during each menstrual cycle in women's reproductive life. The post-menopausal endometrium responds exogenously estrogen-like [3]. Schwab et al expressed that clonogenic stromal and epithelial cells are present in the inactive endometrium.…”

Caprine Endometrial Mesenchymal Stromal Stem Cell: Multilineage Potential, Characterization, and Growth Kinetics in Breeding and Anestrous Stages

“…The endometrium of the uterus in mammals is capable of high and periodic self-renewal regeneration. Also, reconstruction of the endometrium after parturition and rapid proliferation and restoration indicates that the endometrium can be a rich source of MSCs [17]. On the other hand, larger amounts of MSCs are needed for use in clinical and experimental applications than the starting population isolated MSCs which must be expanded in vitro .…”