Document Detail


Positioning of bone marrow hematopoietic and stromal cells relative to blood flow in vivo: serially reconstituting hematopoietic stem cells reside in distinct nonperfused niches.
MedLine Citation:
PMID:  20393133     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Hematopoietic stem cell (HSC) niches have been reported at the endosteum or adjacent to bone marrow (BM) vasculature. To investigate functional attributes of these niches, mice were perfused with Hoechst 33342 (Ho) in vivo before BM cell collection in presence of pump inhibitors and antibody stained. We report that the position of phenotypic HSCs, multipotent and myeloid progenitors relative to blood flow, follows a hierarchy reflecting differentiation stage, whereas mesenchymal stromal cells are perivascular. Furthermore, during granulocyte colony-stimulating factor-induced mobilization, HSCs migrated closer to blood flow, whereas stromal cells did not. Interestingly, phenotypic Lin(-)Sca1(+)KIT(+)CD41(-)CD48(-)CD150(+) HSCs segregated into 2 groups (Ho(neg) or Ho(med)), based on degree of blood/Ho perfusion of their niche. HSCs capable of serial transplantation and long-term bromodeoxyuridine label retention were enriched in Ho(neg) HSCs, whereas Ho(med) HSCs cycled more frequently and only reconstituted a single host. This suggests that the most potent HSC niches are enriched in locally secreted factors and low oxygen tension due to negligible blood flow. Importantly, blood perfusion of niches correlates better with HSC function than absolute distance from vasculature. This technique enables prospective isolation of serially reconstituting HSCs distinct from other less potent HSCs of the same phenotype, based on the in vivo niche in which they reside.
Authors:
Ingrid G Winkler; Valérie Barbier; Robert Wadley; Andrew C W Zannettino; Sharon Williams; Jean-Pierre Lévesque
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-04-14
Journal Detail:
Title:  Blood     Volume:  116     ISSN:  1528-0020     ISO Abbreviation:  Blood     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-07-23     Completed Date:  2010-08-20     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  375-85     Citation Subset:  AIM; IM    
Affiliation:
Biotherapy Program, Mater Medical Research Institute, South Brisbane, Australia.
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MeSH Terms
Descriptor/Qualifier:
Animals
Benzimidazoles
Blood Flow Velocity
Bone Marrow / blood supply*,  drug effects
Bone Marrow Cells / cytology,  physiology
Bromodeoxyuridine / metabolism
Cell Differentiation
Cell Hypoxia
Fluorescent Dyes
Granulocyte Colony Stimulating Factor, Recombinant / administration & dosage
Hematopoietic Stem Cell Mobilization
Hematopoietic Stem Cells / cytology*,  physiology
Mice
Mice, Congenic
Mice, Inbred C57BL
Multipotent Stem Cells / cytology,  physiology
Myeloid Progenitor Cells / cytology,  physiology
Phenotype
Stromal Cells / cytology,  physiology
Chemical
Reg. No./Substance:
0/Benzimidazoles; 0/Fluorescent Dyes; 0/Granulocyte Colony Stimulating Factor, Recombinant; 23491-52-3/HOE 33342; 59-14-3/Bromodeoxyuridine
Comments/Corrections
Comment In:
Blood. 2010 Jul 22;116(3):307-8   [PMID:  20651077 ]

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