Endometrial side population cells: potential adult stem/progenitor cells in endometrium

Uterine endometrium is one of the most important organs for species preservation. However, the physiology of human endometrium remains poorly understood, because the human endometrium undergoes rapid and large changes during each menstrual cycle and it is very difficult to investigate human endometrium as one organ. This remarkable regenerative capacity of human endometrium strongly suggests the existence of adult stem cells, and physiology of endometrium cannot be explained without adult stem cells. Therefore, investigating endometrial stem/progenitor cells should lead to a breakthrough in understanding the normal endometrial physiology and the pathophysiology of endometrial neoplastic disorders, such as endometriosis and endometrial cancer. Several cell populations have been discovered as putative endometrial stem/progenitor cells. Emerging evidence reveals that the endometrial side population (SP) is one of the potential endometrial stem/progenitor populations. Of all the endometrial stem/progenitor cell candidates, the endometrial SP (ESP) is best investigated in vitro and in vivo, and has the largest number of references. In this review, we provide an overview of the accumulating evidence for the ESP cells, both directly from human endometria and from cultured endometrial cells. Furthermore, SP cells are compared to other potential stem/progenitor cells, and we discuss their stem cell properties. We also discuss the difficulties and unsolved issues in endometrial stem cell biology.