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Leukemia (2010) 24, 19791992& 2010 Macmillan Publishers Limited All rights reserved 0887-6924/10
http://www.nature.com/leu
Web End =www.nature.com/leu
SPOTLIGHT REVIEW
The endosteal osteoblastic niche and its role in hematopoietic stem cell homing
and mobilization
J-P Lvesque1,2, FM Helwani1 and IG Winkler1
1Biotherapies Program, Haematopoietic Stem Cell Laboratory, Mater Medical Research Institute, South Brisbane, Queensland, Australia and 2School of Medicine, University of Queensland, Brisbane, Queensland, Australia
The concept of hematopoietic stem cell (HSC) niche was formulated in 1978, but HSC niches remained unidentied for the following two decades largely owing to technical limitations. Sophisticated live microscopy techniques and genetic manipulations have identied the endosteal region of the bone marrow (BM) as a preferential site of residence for the most potent HSC able to reconstitute in serial transplants with osteoblasts and their progenitors as critical cellular elements of these endosteal niches. This article reviews the path to the discovery of these endosteal niches (often called osteoblastic niches) for HSC, what cell types contribute to these niches with their known physical and biochemical features. In the past decade, a rst wave of research uncovered many mechanisms responsible for HSC homing to, and mobilization from, the whole BM tissue. However, the recent discovery of endosteal HSC niches has initiated a second wave of research focusing on the mechanisms by which most primitive HSC lodge into and migrate out of their endosteal niches. The second part of this article reviews the current knowledge of the mechanisms of HSC lodgment into, retention in and mobilization from osteoblastic niches.
Leukemia (2010) 24, 19791992; doi:http://dx.doi.org/10.1038/leu.2010.214
Web End =10.1038/leu.2010.214 ; published online 23 September 2010Keywords: hematopoietic stem cell; niche; osteoblast; bone marrow; homing; mobilization
SPOTLIGHT
Introduction
Following the discovery that virtually all long-term reconstituting hematopoietic activity is contained within the bone marrow (BM) tissue in adult mammals,1,2 many aspects of hematopoietic stem cell (HSC) regulation within the BM have now been elucidated. Some of the most signicant discoveries have been that (1) HSC must reside in specialized niches in the BM to exert their function properly,3 and (2) a small proportion of HSC and more committed hematopoietic progenitors cells (HPC) physiologically trafc continually from the BM into the circulation4 and concomitantly re-home to the BM.5 Although little is known about the mechanisms leading to the spontaneous...