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Niche recycling through division-independent egress of hematopoietic stem cells

Bhattacharya, Deepta; Czechowicz, Agnieszka; Ooi, A. G. Lisa; Rossi, Derrick J.; Bryder, David LU and Weissman, Irving L. (2009) In Journal of Experimental Medicine 206(12). p.2837-2850
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 similar to 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.... (More)
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 similar to 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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Experimental Medicine
volume
206
issue
12
pages
2837 - 2850
publisher
Rockefeller University Press
external identifiers
  • wos:000272079300020
  • scopus:73349143984
ISSN
1540-9538
DOI
10.1084/jem.20090778
language
English
LU publication?
yes
id
03d50bf2-1be4-4980-8680-590704b4a604 (old id 1518264)
date added to LUP
2010-01-08 14:45:40
date last changed
2017-11-12 03:47:40
@article{03d50bf2-1be4-4980-8680-590704b4a604,
  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 similar to 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.},
  author       = {Bhattacharya, Deepta and Czechowicz, Agnieszka and Ooi, A. G. Lisa and Rossi, Derrick J. and Bryder, David and Weissman, Irving L.},
  issn         = {1540-9538},
  language     = {eng},
  number       = {12},
  pages        = {2837--2850},
  publisher    = {Rockefeller University Press},
  series       = {Journal of Experimental Medicine},
  title        = {Niche recycling through division-independent egress of hematopoietic stem cells},
  url          = {http://dx.doi.org/10.1084/jem.20090778},
  volume       = {206},
  year         = {2009},
}