Endometrial Stem Cell Markers: Current Concepts and Unresolved Questions

Abstract

The human endometrium is a highly regenerative organ undergoing over 400 cycles of shedding and regeneration over a woman's lifetime. Menstrual shedding and the subsequent repair of the functional layer of the endometrium is a process unique to humans and higher-order primates. This massive regenerative capacity is thought to have a stem cell basis, with human endometrial stromal stem cells having already been extensively studied. Studies on endometrial epithelial stem cells are sparse, and the current belief is that the endometrial epithelial stem cells reside in the terminal ends of the basalis glands at the endometrial/myometrial interface. Since almost all endometrial pathologies are thought to originate from aberrations in stem cells that regularly regenerate the functionalis layer, expansion of our current understanding of stem cells is necessary in order for curative treatment strategies to be developed. This review critically appraises the postulated markers in order to identify endometrial stem cells. It also examines the current evidence supporting the existence of epithelial stem cells in the human endometrium that are likely to be involved both in glandular regeneration and in the pathogenesis of endometrial proliferative diseases such as endometriosis and endometrial cancer.

Keywords: adult stem cells; endometrial cancer; endometrial regeneration; endometriosis; endometrium; stem cell markers.

Figure 1

(A): Low power (100×) micrograph of full thickness biopsy of human endometrium and sub-endometrial myometrium stained with Hematoxylin and Eosin. (B): Representative micrograph depicting the distinct anatomical areas in the human endometrium, luminal epithelium, functionalis, and basalis (magnification 400×).

Figure 2

Hormone dependent regulation of the ratio of cell types in the endometrium (Abbreviations ST-cell—stem cell, E2-cell—oestrogen sensitive cell, E2P-cell—oestrogen-progesterone sensitive cell, P-cell—progesterone sensitive cell). Figure adapted from Reference [11].