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PMID: 19887396 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Niche recycling through division-independent egress of hematopoietic stem cells.

The Journal of experimental medicine ·Vol. 206 ·No. 12 ·2009-11-23 ·Pages 2837-50

Bhattacharya D, Czechowicz A, Ooi AG, Rossi DJ, Bryder D, Weissman IL

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 approximately 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.

MeSH Terms
Animals Bone Marrow/physiology Hematopoietic Stem Cell Transplantation Hematopoietic Stem Cells/cytology,physiology Mice Mice, Transgenic Transplantation, Homologous
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Bhattacharya Deepta
Institute of Stem Cell Biology and Regenerative Medicine Stanford University School of Medicine Stanford, CA 94305, USA. deeptab@wustl.edu
Czechowicz Agnieszka
Ooi A G Lisa
Rossi Derrick J
Bryder David
Weissman Irving L
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
1540-9538
DOI
10.1084/jem.20090778
Email
deeptab@wustl.edu
Published
2009-11-23
Epub
2009-00-02
Pages
2837-50
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2806613
Subset
IM
Grants
NIAID NIH HHS · T32 AI007290 · United States
NCI NIH HHS · R01CA086065 · United States
NIDDK NIH HHS · K01 DK078318-02 · United States
NHLBI NIH HHS · R01HL058770 · United States
Howard Hughes Medical Institute · United States
PHS HHS · R00AGO29760 · United States
NIDDK NIH HHS · K01DK078318 · United States
NHLBI NIH HHS · R01 HL058770 · United States
NIDDK NIH HHS · K01 DK078318-03 · United States
NIDDK NIH HHS · K01 DK078318 · United States
NIAID NIH HHS · T32AI0729022 · United States
NCI NIH HHS · R01 CA086065 · United States
NIDDK NIH HHS · K01 DK078318-01 · United States
External Links
PubMed source DOI: 10.1084/jem.20090778 PMC Full Text View journal details
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