Regeneration Potential of Stem Cell Systems in the Human Female Reproductive Tract.

The human uterus is unique in that it exhibits a tremendous regenerative capacity that enables cyclical regeneration and remodeling throughout a woman's reproductive life. This plasticity of the reproductive system has recently been highlighted. We showed that functional endometrial tissue could be regenerated from only a small number of singly dispersed human endometrial cells, when they were transplanted beneath the kidney capsule of severely immunodeficient mice. This artificially generated endometrium resembles the natural endometrium, and contains human blood vessels which invade the mouse kidney parenchyma. Additionally, it mimics normal hormone-dependent changes including proliferation, differentiation, and tissue breakdown (menstruation). The regenerative capacity of endometrial cells makes them ideal candidates for tissue reconstitution, angiogenesis, and human-mouse chimeric vessel formation. The smooth muscle cells of the uterus (myometrium) share the plasticity of the endometrium. This is evidenced by their capacity for dramatic, repeatable, pregnancy-induced enlargement. Regeneration and remodeling in the female reproductive tract allude to the existence of endometrial and myometrial stem cell systems. Endometrial stem cells have already been described; however, no myometrial stem cells have been identified to date. We have recently isolated candidate populations of adult stem cells from both the human endometrium and myometrium using a Hoechst "side population" method. Characterization of these stem-like cells, along with the study of the mechanisms controlling their regeneration, will improve the understanding of the physiology and pathophysiology of the female reproductive tract. Additionally, myometrial and endometrial stem-like cells might also represent a novel source of biological materials that could be used for the reconstruction of not only the human uterine components but other tissues/organs as well. References: Masuda H, Maruyama T, Hiratsu E, et al. Proc Natl Acad Sci USA. 2007;104:1925-30. Ono M, Maruyama T, Masuda H, et al. Proc Natl Acad Sci USA. 2007;104:18700-5.