Tissue-specific stem cells in the myometrium and tumor-initiating cells in leiomyoma.
Tissue-specific (or somatic) stem cells constitute a subset of cells residing in normal adult tissues. By undergoing asymmetric division, they retain their ability to self-renew while producing daughter cells that go on to differentiate and play a role in tissue regeneration and repair. The human uterus consists primarily of endometrium and myometrium (the smooth muscle layer) that rapidly enlarges through its tremendous regenerative and remodeling capacity to accommodate the developing fetus. Such uterine enlargement and remodeling can take place repeatedly and cyclically over the course of a woman's reproductive life. These unique properties of the uterus suggest the existence of endometrial and myometrial stem cell systems. In addition, like somatic cells, tumor stem cells or tumor-initiating cells, a subset of cells within a tumor, retain the ability to reconstitute tumors. Uterine smooth muscle cells are thought to be the origin of leiomyomas that are the most common type of gynecologic tumor. Recent work has identified, isolated, and characterized putative stem/progenitor cells in the myometrium and in leiomyomas. Here, we review current studies of myometrial and leiomyoma stem/progenitor cells and provide a new paradigm for understanding myometrial physiology and pathology and how these cells might contribute to uterine remodeling during pregnancy and the formation of leiomyomas. The role of the WNT/CTNNB1 pathway in the pathogenesis of leiomyoma is also discussed.
Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan.
Masanori
M
Ono
Department of Obstetrics and Gynecology, Feinberg School of Medicine at Northwestern University, Chicago, Illinois.
Serdar E
SE
Bulun
Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan tetsuo@a5.keio.jp.
Tetsuo
T
Maruyama
D000328:Adult; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007889:Leiomyoma / Q000473:pathology*; D009215:Myometrium / Q000166:cytology* / Q000473:pathology / Q000502:physiology; D014411:Neoplastic Stem Cells / Q000473:pathology*; D009928:Organ Specificity; D011247:Pregnancy; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D014594:Uterine Neoplasms / Q000473:pathology*
leiomyoma; myometrium; pregnancy; regeneration; tissue-specific stem cells; tumor-initiating cells