The relationship between bone, hemopoietic stem cells, and vasculature

Blood - Tập 118 - Trang 1516-1524 - 2011
Sarah L. Ellis1,2, Jochen Grassinger3,4, Allan Jones5, Judy Borg1, Todd Camenisch6, David Haylock7, Ivan Bertoncello2, Susan K. Nilsson2,7
1Peter MacCallum Cancer Centre, Melbourne, Australia
2University of Melbourne, Parkville, Australia
3University of Regensburg Medical Centre, Regensburg, Germany;
4Australian Stem Cell Centre, Clayton, Australia
5University of Sydney, Sydney, Australia
6College of Pharmacy, University of Arizona, Tucson, AZ; and
7Commonwealth Scientific and Industrial Research Organisation, Clayton, Australia

Tóm tắt

Abstract A large body of evidence suggests hemopoietic stem cells (HSCs) exist in an endosteal niche close to bone, whereas others suggest that the HSC niche is intimately associated with vasculature. In this study, we show that transplanted hemopoietic stem and progenitor cells (HSPCs) home preferentially to the trabecular-rich metaphysis of the femurs in nonablated mice at all time points from 15 minutes to 15 hours after transplantation. Within this region, they exist in an endosteal niche in close association with blood vessels. The preferential homing of HSPCs to the metaphysis occurs rapidly after transplantation, suggesting that blood vessels within this region may express a unique repertoire of endothelial adhesive molecules. One candidate is hyaluronan (HA), which is highly expressed on the blood vessel endothelium in the metaphysis. Analysis of the early stages of homing and the spatial dis-tribution of transplanted HSPCs at the single-cell level in mice devoid of Has3-synthesized HA, provides evidence for a previously undescribed role for HA expressed on endothelial cells in directing the homing of HSPCs to the metaphysis.

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