The Elusive Endometrial Epithelial Stem/Progenitor Cells

Abstract

The human endometrium undergoes approximately 450 cycles of proliferation, differentiation, shedding and regeneration over a woman’s reproductive lifetime. The regenerative capacity of the endometrium is attributed to stem/progenitor cells residing in the basalis layer of the tissue. Mesenchymal stem cells have been extensively studied in the endometrium, whereas endometrial epithelial stem/progenitor cells have remained more elusive. This review details the discovery of human and mouse endometrial epithelial stem/progenitor cells. It highlights recent significant developments identifying putative markers of these epithelial stem/progenitor cells that reveal their in vivo identity, location in both human and mouse endometrium, raising common but also different viewpoints. The review also outlines the techniques used to identify epithelial stem/progenitor cells, specifically in vitro functional assays and in vivo lineage tracing. We will also discuss their known interactions and hierarchy and known roles in endometrial dynamics across the menstrual or estrous cycle including re-epithelialization at menses and regeneration of the tissue during the proliferative phase. We also detail their potential role in endometrial proliferative disorders such as endometriosis.

Endometrial stem/progenitor cells and their roles in immunity, clinical application, and endometriosis

“…In addition, Axin2 + cells can form fully functional endometrial organoids in vitro [ 107 ]. The above findings seem to provide evidence for the involvement of the mesenchymal-to-epithelial transition (MET) in the maintenance and regeneration of the uterine epithelium [ 109 ]. However, a recent cell fate tracing study found that the conclusive evidence for the conversion of mesenchymal cells to epithelial cells in adult uterine is lacking.…”

The New Era of Three-Dimensional Histoarchitecture of the Human Endometrium

“…We found that the plexus network remained behind in all menstrual samples observed, which demonstrates that this is a major component of the basalis ( Figure 3 , Video S2 ). Although previous scanning electron microscope studies have shown that the endometrium sheds in a piecemeal manner with denuded and intact sections next to each other [ 42 ], our study has demonstrated that the functional layer of the endometrium sheds off completely during menstruation, probably due to a limited area where we assessed 3D structure [ 29 ].…”

Trophic And Immunomodulatory Effects of Adipose Tissue-Derived Stem Cells In A Preclinical Murine Model of Endometriosis

“…ASC infusion also decreased pro-in ammatory and probrotic cytokine expression but did not alter the expression of anti-in ammatory cytokines, matrix metalloproteases, angiogenetic factors, or estrogen and progesterone receptors. Endometrial stem cells, which are located in the basalis layer, differentiate into the endometrial stroma, epithelium, and endothelium [39]. After the infusion of bone-marrow cells with mTert-GFP or Ch β-actin GFP, all GFP-positive cells in the endometrium are immune cells, including T cells and macrophages, suggesting that bone-marrow stem cells do not contribute to endometrial cell lineages [40].…”