The human endometrium undergoes >400 cycles of growth, differentiation and shedding during a womans reproductive years. Endometrial regeneration is likely mediated by stem/progenitor cells. Emerging evidence suggests that disorders associated with abnormal endometrial proliferation (endometriosis, endometrial cancer) may involve endometrial stem/progenitor cells. In human endometrium, colony forming units (CFU), side population (SP) cells and tissue reconstituting cells have been identified. Individual CFUs undergo self-renewal and have high proliferative capacity. Epithelial CFUs differentiate into gland-like structures and stromal CFUs have a mesenchymal stem cell (MSC) phenotype and differentiate into mesodermal lineages, typical of MSC. This suggests that human endometrium contains small populations of epithelial progenitors and MSC. Gene expression profiling of purified endometrial epithelial cells from pre- and post-menopausal women has identified a candidate marker for endometrial epithelial progenitor cells. Endometrial MSC (eMSC) can be prospectively isolated from tissue in the CD140bCD146 fraction or using a novel single marker, W5C5. These markers show that the epithelial progenitors are found in the endometrial basalis while eMSC are located perivascularly in both functionalis and basalis. Using these markers we show that epithelial progenitors and eMSC are shed in menstrual blood, and in women with endometriosis, endometrial W5C5 MSC are preferentially shed into the pelvic cavity during menstruation, where they may initiate endometriosis lesions. We are examining the utility of autologous eMSC as a cell-based therapy for pelvic organ prolapse, an intractable disorder resulting from herniation of the pelvic organs into the vagina due to childbirth injury. In a nude rat model of fascial repair, we have shown that polyamide mesh seeded with eMSC promoted early neovascularisation, an M2 macrophage wound healing response, deposition of non-scarring collagen and improved biomechanical properties of the mesh/tissue complex compared with mesh alone. These studies demonstrate that human endometrium provides an alternate source of MSC for cell-based therapies.
02 Sep 2014 - 04 Sep 2014