Niche recycling through division-independent egress of hematopoietic stem cells
Författare
Summary, in English
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.
Avdelning/ar
- Immunology
Publiceringsår
2009
Språk
Engelska
Sidor
2837-2850
Publikation/Tidskrift/Serie
Journal of Experimental Medicine
Volym
206
Issue
12
Dokumenttyp
Artikel i tidskrift
Förlag
Rockefeller University Press
Ämne
- Immunology in the medical area
Status
Published
Forskningsgrupp
- Immunology
ISBN/ISSN/Övrigt
- ISSN: 1540-9538