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https://hdl.handle.net/2440/76137
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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 |
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