Publication: Niche Recycling through Division-Independent Egress of Hematopoietic Stem Cells
Open/View Files
Date
2009
Published Version
Journal Title
Journal ISSN
Volume Title
Publisher
The Rockefeller University Press
The Harvard community has made this article openly available. Please share how this access benefits you.
Citation
Bhattacharya, Deepta, Agnieszka Czechowicz, A. G. Lisa Ooi, Derrick J. Rossi, David Bryder, and Irving L. Weissman. 2009. Niche recycling through division-independent egress of hematopoietic stem cells. The Journal of Experimental Medicine 206(12): 2837-2850.
Research Data
Abstract
Hematopoietic stem cells (HSCs) are thought to reside in discrete niches through stable adhesion, yet previous studies have suggested that host HSCs can be replaced by transplanted donor HSCs, even in the absence of cytoreductive conditioning. To explain this apparent paradox, we calculated, through cell surface phenotyping and transplantation of unfractionated blood, that ∼1–5% of the total pool of HSCs enters into the circulation each day. Bromodeoxyuridine (BrdU) feeding experiments demonstrated that HSCs in the peripheral blood incorporate BrdU at the same rate as do HSCs in the bone marrow, suggesting that egress from the bone marrow to the blood can occur without cell division and can leave behind vacant HSC niches. Consistent with this, repetitive daily transplantations of small numbers of HSCs administered as new niches became available over the course of 7 d led to significantly higher levels of engraftment than did large, single-bolus transplantations of the same total number of HSCs. These data provide insight as to how HSC replacement can occur despite the residence of endogenous HSCs in niches, and suggest therapeutic interventions that capitalize upon physiological HSC egress.
Description
Other Available Sources
Keywords
Terms of Use
This article is made available under the terms and conditions applicable to Other Posted Material (LAA), as set forth at Terms of Service