The stem cell niche in health and leukemic disease.
That adult stem cells live in a highly specialized complex microenvironment, also known as a niche, is a pedestrian concept about 30 years old. It may, however, represent a relatively novel approach to being able to modify either normal or abnormal stem cells. Our emphasis in the past has been focused on identifying autonomous regulators of the stem cells and in attempting to modify them through the use of exogenous agents like cytokines. The body modulates these cells largely through the complex system that is embodied in the niche. This report discusses studies in which the niche components are modified to observe their effect on stem cells. The niches being investigated lie in the gut, skin, brain and bone. Other sites for hematopoiesis exist in the body, but these specific microenvironments can be localized and each component can be carefully evaluated using mouse models. Studies are ongoing as to how the stem cell microenvironment can support or propagate malignancies. By understanding the signals of this particular microenvironment, we may be able to adapt them to achieve a therapeutic benefit.
Scadden
David T
DT
Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. scadden.david@mgh.harvard.edu
D000818:Animals; D004195:Disease Models, Animal; D016326:Extracellular Matrix Proteins / Q000502:physiology*; D015973:Gene Expression Regulation, Leukemic / Q000502:physiology; D006801:Humans; D007938:Leukemia / Q000378:metabolism*; D051379:Mice; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000378:metabolism*
D016326:Extracellular Matrix Proteins