Abstract
BackgroundThe human endometrium undergoes cyclical regeneration throughout a woman's reproductive life. Ectopic implantation of endometrial cells through retrograde menstruation gives rise to endometriotic lesions which affect approximately 10% of reproductive-aged women. The high regenerative capacity of the human endometrium at eutopic and ectopic sites suggests the existence of stem/progenitor cells and a unique angiogenic system. The objective of this study was to isolate and characterize putative endometrial stem/progenitor cells and to address how they might be involved in the physiology of endometrium.Methodology/Principal FindingsWe found that approximately 2% of the total cells obtained from human endometrium displayed a side population (SP) phenotype, as determined by flow cytometric analysis of Hoechst-stained cells. The endometrial SP (ESP) cells exhibited preferential expression of several endothelial cell markers compared to endometrial main population (EMP) cells. A medium specific for endothelial cell culture enabled ESP cells to proliferate and differentiate into various types of endometrial cells, including glandular epithelial, stromal and endothelial cells in vitro, whereas in the same medium, EMP cells differentiated only into stromal cells. Furthermore, ESP cells, but not EMP cells, reconstituted organized endometrial tissue with well-delineated glandular structures when transplanted under the kidney capsule of severely immunodeficient mice. Notably, ESP cells generated endothelial cells that migrated into the mouse kidney parenchyma and formed mature blood vessels. This potential for in vivo angiogenesis and endometrial cell regeneration was more prominent in the ESP fraction than in the EMP fraction, as the latter mainly gave rise to stromal cells in vivo.Conclusions/SignificanceThese results indicate that putative endometrial stem cells are highly enriched in the ESP cells. These unique characteristics suggest that ESP cells might drive physiological endometrial regeneration and be involved in the pathogenesis of endometriosis.
Highlights
Human endometrium, which lines the uterine cavity, exhibits unique properties of cyclical regeneration and tissue breakdown under the influence of estrogen and progesterone throughout the course of a woman’s reproductive life
The findings presented here strongly support the idea that the basalis of the endometrium harbors stem/progenitor cells responsible for endometrial regeneration during menses as well as after parturition in both women and menstruating non-human primates [23]
A relatively small number of dispersed human endometrial cells containing endometrial SP (ESP) cells can generate functional endometrial tissue comprising glands, stroma, immune cells and vascular components when they are transplanted under the kidney capsule of severely immunodeficient mice [1]
Summary
Human endometrium, which lines the uterine cavity, exhibits unique properties of cyclical regeneration and tissue breakdown under the influence of estrogen and progesterone throughout the course of a woman’s reproductive life. When single cell suspensions of endometrial cells are transplanted under the kidney capsule of severely immunodeficient NOD/SCID/ccnull (NOG) mice [1], the reconstructed ectopic endometrial tissues show menstrual cyclerelated morphological and functional changes repeatedly in response to treatment with estrogen and progesterone [1]. These unique properties reflect the remarkable capacity of human endometrial cells for regeneration at eutopic and ectopic locations, and suggest the existence of stem/progenitor cells as well as an angiogenic system in the human endometrium.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
