Epithelial progenitor cells in human endometrium and endometriosis

2017-02-03T03:40:26Z (GMT) by Tan, Charmaine
The human endometrium is a highly regenerative tissue that undergoes rapid repair and restoration following menstruation and parturition. Endometrial stem/progenitor cells have been hypothesised to be responsible for this. Despite evidence for endometrial epithelial progenitor cells, there are currently no known markers for their prospective identification. The aim of this thesis was to identify a candidate marker by screening endometrial cells against a panel of known and novel antibodies for immunoreactivity by flow cytometry and immunohistochemistry. H3 was identified as a priority and was assessed for its ability to be a candidate marker. Endometrial epithelial cells were flow cytometry sorted into subpopulations based upon the relative expression of H3 and EpCAM (an epithelial marker). These subpopulations were assessed for stem/progenitor cell properties using functional assays. This thesis demonstrates for the first time that H3 and EpCAM are putative markers that enrich for endometrial epithelial progenitor cells that are clonogenic and undergo self-renewal in vitro. This thesis also investigated the role that endometrial stem/progenitor cells may have in the development of endometriosis. Shedding endometrium and peritoneal fluid were collected from menstruating women with and without endometriosis and assessed for presence of endometrial stem/progenitor cells. Clonal studies did not support the hypothesis that endometriosis is established because of the erroneous shedding of endometrial stem/progenitor cells during menstruation. This was in contrast to preliminary flow cytometry results that detected an increased expression of putative endometrial stem/progenitor cell markers (H3 and W5C5) in samples collected from endometriosis women. Further studies will investigate this. The findings of this thesis have identified a putative marker that will enable further identification of endometrial epithelial progenitor cell markers in future. These markers will allow further characterisation of this rare population and investigations into their potential role in gynaecological disorders such as endometriosis. The current aetiology of endometriosis remains unknown. The identification of endometrial clonogenic cells within endometriotic lesions will provide future examination into what factors in peritoneal fluid may support ectopic endometrial growth so that improvements in treatment can be made.