Stem/progenitor cells and the regeneration potentials in the human uterus
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REVIEW ARTICLE
Stem/progenitor cells and the regeneration potentials in the human uterus Tetsuo Maruyama
Received: 20 June 2009 / Accepted: 4 August 2009 / Published online: 26 August 2009 Ó Japan Society for Reproductive Medicine 2009
Abstract The human uterus is unique in that it possesses the tremendous regenerative capacity required for cyclical regeneration and remodeling throughout a woman’s reproductive life. Not only must the uterus rapidly enlarge to accommodate the developing fetus, the endometrium must also regenerate with each menstrual cycle. This plasticity of the reproductive system has recently been highlighted. My research group and collaborators showed that functional endometrial tissue could be regenerated from only a small number of singly dispersed human endometrial cells, transplanted beneath the kidney capsule of severely immunodeficient mice. This artificially generated endometrium resembles the natural endometrium, and contains human blood vessels that invade the mouse kidney parenchyma. Additionally, it mimics normal hormonedependent 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. We have recently isolated candidate populations of adult stem cells from both the human endometrium and myometrium. Characterization of these endometrial and myometrial cells, along with the study of the mechanisms
T. Maruyama (&) Department of Obstetrics and Gynecology, Keio University School of Medicine, 35, Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan e-mail: [email protected]
controlling their regeneration, will improve the understanding of the physiology and pathophysiology of the female reproductive tract. Furthermore, myometrial and endometrial stem-like cells might also represent a novel source of biological material that could be used for the reconstruction of not only the human uterus but other organs as well. Keywords Endometrium Myometrium Stem cell Side population Regeneration
Introduction Dramatic advances in stem cell biology and regenerative medicine have promoted not only the establishment of a research framework for the discovery of novel paradigms in cell lineage commitment, but also the development of therapeutics to be used in the treatment of diseases that result from abnormal cellular function and the destruction of tissue. The goal of the regenerative medicine-based therapies is to repair damaged and diseased tissues by providing replacement cells or factors that can restore tissue function. To date, embryonic stem cells, induced pluripotent cells, and adult s
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