Hematopoietic Stem Cell Niches Extrinsic Regulation of HSCs

The stem cell niche was initially proposed in 1978 as a protective physiological microenvironment that maintains the stem cell in quiescence for self-renewal but can activate the stem cell to proliferate and differentiate to maintain and repair tissue (Schofield 1978). The fact that bone marrow is located within bone cavities suggests that the two tissues interact, providing a protective environment for the HSCs (Li and Li 2006). Recently it has been proposed that more than one niche may exist: the endosteal bone marrow niche, which primarily supports HSCs in steady-state hematopoiesis and maintains HSC quiescence, and a vascular bone marrow niche, which supports HSCs at the fenestrated endothelium of bone marrow sinusoids and allows self-renewing HSCs to access the vasculature. The vascular niche may function as a secondary niche, which requires HSCs to migrate from the primary endosteal niche (Wilson and Trump 2006). Despite the fact that most adult HSCs reside in the bone marrow, administration of 89Sr eliminates, by local irradiation, endosteal niches and results in splenic hematopoiesis (Klassen 1972). This suggests that, although HSCs require a supportive microenvironment, they are not passive residents and can perhaps modify extramedullary niches to enhance support of hematopoiesis outside the bone marrow. The capacity for influencing or remodeling the niche, as we will discuss in a later portion of the chapter, is also an important property of metastatic cancer cells.

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