Adult Stem Cells in the Pathogenesis and Treatment of Endometriosis

Abstract

The human endometrium is a dynamic tissue that undergoes approximately 400 cyclical episodes of proliferation, differentiation, shedding, and regeneration in a woman's reproductive lifespan. The regenerative capacity of human endometrium is likely mediated by adult stem cells. At the cellular level, endometrial mesenchymal stem/stromal cells, located in both the functionalis and basalis layers, support regeneration of the stromal vascular compartment and epithelial progenitor cells, postulated to reside in the basalis epithelium, likely regenerate the glands. Bone marrow adult stem cells, including endothelial progenitor cells, may also participate. Endometriosis can be considered an endometrial proliferative disorder due to dysregulation of the cellular and molecular regenerative processes. Endometriosis is primarily thought to occur via retrograde menstruation of endometrial debris. It is postulated that endometrial stem/progenitor cells, which have been identified in menstrual blood, are shed into the peritoneal cavity where they adhere to pelvic organs and initiate endometriotic lesions. The homing of bone-marrow-derived adult stem cells to endometriotic lesions is thought to drive progression of the disease. New drug therapies are urgently required for the treatment of endometriosis due to frequent disease recurrence with current surgical or medical treatments. Medications directly targeting endometrial stem/progenitor cells during menstruation, or following surgery, or targeting bone marrow cell trafficking, are potential targets for future therapies to manage disease initiation and progression. In this review, we will summarize the current literature on adult stem cell contributions to the development of endometriosis and will then examine the current potential therapies that may target endometrial stem/progenitor cells.