title: Niche recycling through division-independent egress of hematopoietic stem cells.
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.
authors.affiliation: Institute of Stem Cell Biology and Regenerative Medicine Stanford University School of Medicine Stanford, CA 94305, USA. deeptab@wustl.edu
authors.forename: Deepta
authors.initials: D
authors.lastname: Bhattacharya
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Czechowicz
authors.forename: A G Lisa
authors.initials: AG
authors.lastname: Ooi
authors.forename: Derrick J
authors.initials: DJ
authors.lastname: Rossi
authors.forename: David
authors.initials: D
authors.lastname: Bryder
authors.forename: Irving L
authors.initials: IL
authors.lastname: Weissman
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000502:physiology*; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D014184:Transplantation, Homologous