Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/76137
Citations
Scopus Web of Science® Altmetric
?
?
Type: Journal article
Title: Sphingosine-1-phosphate facilitates trafficking of hematopoietic stem cells and their mobilization by CXCR4 antagonists in mice
Author: Juarez, J.
Harun, N.
Thien, M.
Welschinger, R.
Baraz, R.
Dela Pena, A.
Pitson, S.
Rettig, M.
DiPersio, J.
Bradstock, K.
Bendall, L.
Citation: Blood, 2012; 119(3):707-716
Publisher: Amer Soc Hematology
Issue Date: 2012
ISSN: 0006-4971
1528-0020
Statement of
Responsibility: 
Julius G. Juarez, Nadia Harun, Marilyn Thien, Robert Welschinger, Rana Baraz, Aileen Dela Pena, Stuart M. Pitson, Michael Rettig, John F. DiPersio, Kenneth F. Bradstock, and Linda J. Bendall
Abstract: CXCL12 and VCAM1 retain hematopoietic stem cells (HSCs) in the BM, but the factors mediating HSC egress from the BM to the blood are not known. The sphingosine-1-phosphate receptor 1 (S1P₁) is expressed on HSCs, and S1P facilitates the egress of committed hematopoietic progenitors from the BM into the blood. In the present study, we show that both the S1P gradient between the BM and the blood and the expression of S1P₁ are essential for optimal HSC mobilization by CXCR4 antagonists, including AMD3100, and for the trafficking of HSCs during steady-state hematopoiesis. We also demonstrate that the S1P₁ agonist SEW2871 increases AMD3100-induced HSC and progenitor cell mobilization. These results suggest that the combination of a CXCR4 antagonist and a S1P₁ agonist may prove to be sufficient for mobilizing HSCs in normal donors for transplantation purposes, potentially providing a single mobilization procedure and eliminating the need to expose normal donors to G-CSF with its associated side effects.
Keywords: Hematopoietic Stem Cells
Cells, Cultured
Animals
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Inbred DBA
Mice, Transgenic
Mice, Knockout
Humans
Mice
Mice, SCID
Sphingosine
Benzylamines
Heterocyclic Compounds
Phosphotransferases (Alcohol Group Acceptor)
Lysophospholipids
Oligopeptides
Granulocyte Colony-Stimulating Factor
Receptors, CXCR4
Receptors, Lysosphingolipid
RNA, Messenger
Cytokines
Drug Combinations
Anti-HIV Agents
Blotting, Western
Immunoenzyme Techniques
Prognosis
Hematopoietic Stem Cell Mobilization
Hematopoietic Stem Cell Transplantation
Cell Proliferation
Cell Movement
Drug Synergism
Adult
Aged
Middle Aged
Female
Male
Chemokine CXCL12
Real-Time Polymerase Chain Reaction
Cyclams
Sphingosine-1-Phosphate Receptors
Rights: © 2012 by The American Society of Hematology
DOI: 10.1182/blood-2011-04-348904
Grant ID: http://purl.org/au-research/grants/nhmrc/512431
Published version: http://dx.doi.org/10.1182/blood-2011-04-348904
Appears in Collections:Aurora harvest 4
Molecular and Biomedical Science publications

Files in This Item:
There are no files associated with this item.


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.