PARENT SESSION

(T722) STEM CELL SUPPORT OF UTERINE FUNCTION: IMPLICATIONS FOR CYCLIC REMODELING, PREGNANCY, AND UTERINE DISEASE.

Zhang, Ling¹, Johnson, Joshua¹, Skaznik-Wikiel, Malgorzata¹, Forkert, Randolf ¹, Adams, Gregor ¹, Scadden, David¹, Pru, James¹, ¹ Massachusetts General Hospital/Harvard Medical School, Charlestown, MA, US

ABSTRACT- Dysfunction of the uterus is a common factor affecting the quality of life and morbidity/mortality of the human female. More than 35,000 women (USA) are diagnosed with endometrial cancer annually, and endometriosis, which often results in infertility, affects up to 15% of all reproductive aged women. Recent advances in stem cell biology have made it clear that most tissues are extremely plastic in nature, exhibiting renewal via adult stem cells. Yet there are almost no studies of stem cells in the uterus, an organ that undergoes perhaps the most extensive proliferative changes and remodeling in adult mammals. We hypothesize that a population of adult (uterine) stem cells (USCs) exists that contributes to tissue morphogenesis during the estrous cycle and pregnancy, and that disruption of normal USC function is causal in uterine disease. Initial studies were designed to determine whether cells with stem cell characteristics reside within the mouse uterus. Results from long-term labeling and clonogenicity assays, pulse-chase studies, and immunohistochemical analyses of known stem cell markers all support the identification of a population of USCs that reside within the endometrium. The expression of stem cell markers increases dramatically just prior to and during early pregnancy when the endometrial compartment expands (decidualization). This finding raises the possibility that USCs contribute to the establishment of pregnancy. Bone marrow transplantation experiments provide evidence that USC precursors derive from an extra-uterine source. Microarray analysis and immunohistochemistry confirmed the induction of stem cell mobilization factors in the uterus of the estrous cycle and early pregnancy. Functional studies are underway to assess the contribution of uterine stem cells to normal uterine physiology. The clinical implications of stem cell function during normal uterine remodeling, as well as dysfunction in disease states are now beginning to be addressed. This research is supported by Vincent Memorial Research Funds.

KEY WORDS: stem cell, uterus, development, disease