Niche recycling through division-independent egress of hematopoietic stem cells

Deepta Bhattacharya, Agnieszka Czechowicz, A. G.Lisa Ooi, Derrick J. Rossi, David Bryder, Irving L. Weissman

Research output: Contribution to journalArticlepeer-review

102 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2837-2850
Number of pages14
JournalJournal of Experimental Medicine
Volume206
Issue number12
DOIs
StatePublished - Nov 23 2009
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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