Evidence for the Involvement of Sphingosine-1-Phosphate in the Homing and Engraftment of Hematopoietic Stem Cells to Bone Marrow

Authors

Mateusz Adamiak, University of Louisville
Sylwia Borkowska, University of Louisville
Marcin Wysoczynski, University of Louisville
Malwina Suszynska, University of Louisville
Magda Kucia, University of Louisville
Gregg Rokosh, University of Louisville
Ahmed Abdel-Latif, University of KentuckyFollow
Janina Ratajczak, University of Louisville
Mariusz Z. Ratajczak, University of Louisville

Abstract

The α-chemokine stromal-derived factor 1 (SDF-1), which binds to the CXCR4 receptor, directs migration and homing of CXCR4⁺ hematopoietic stem/progenitor cells (HSPCs) to bone marrow (BM) stem cell niches. Nevertheless, it is also known that CXCR4^-/- fetal liver-derived hematopoietic stem cells engraft into BM and that blockade of CXCR4 by its antagonist AMD3100 does not prevent engraftment of HSPCs. Because of this finding of SDF-1-CXCR4-independent BM homing, the unique role of SDF-1 in HSPC homing has recently been challenged. While SDF-1 is the only chemokine that chemoattracts HSPCs, other chemoattractants for these cells have recently been described, including the bioactive phosphosphingolipid sphingosine-1-phosphate (S1P). To address the potential role of S1P in homing of HSPCs to BM, we performed hematopoietic transplants into mice deficient in BM-expressed sphingosine kinase 1 (Sphk1^-/-) using hematopoietic cells from normal control mice as well as cells from mice in which floxed CXCR4 (CXCR4^fl/fl) was conditionally deleted. We observed the presence of a homing and engraftment defect in HSPCs of Sphk1^-/- mice that was particularly profound after transplantation of CXCR4^-/- BM cells. Thus, our results indicate that BM-microenvironment-expressed S1P plays a role in homing of HSPCs. They also support the concept that, in addition to the SDF-1-CXCR4 axis, other chemotactic axes are also involved in homing and engraftment of HSPCs.

Document Type

Article

Publication Date

8-7-2015

Notes/Citation Information

Published in Oncotarget, v. 6, no. 22, p. 18819-18828.

Copyright @ 2016 Impact Journals, LLC

Licensed under a Creative Commons Attribution 3.0 License.

Digital Object Identifier (DOI)

http://dx.doi.org/10.18632/oncotarget.4710

Funding Information

This work was supported by NIH grants 2R01 DK074720 and R01HL112788 and the Stella and Henry Hoenig Endowment to MZR and University of www.impactjournals.com/oncotarget 18827 Oncotarget Kentucky Clinical and Translational Science Pilot Award (UL1TR000117), the UK COBRE Early Career Program (P20 GM103527), and NIH Grant R56 HL124266.

Repository Citation

Adamiak, Mateusz; Borkowska, Sylwia; Wysoczynski, Marcin; Suszynska, Malwina; Kucia, Magda; Rokosh, Gregg; Abdel-Latif, Ahmed; Ratajczak, Janina; and Ratajczak, Mariusz Z., "Evidence for the Involvement of Sphingosine-1-Phosphate in the Homing and Engraftment of Hematopoietic Stem Cells to Bone Marrow" (2015). Internal Medicine Faculty Publications. 83.
https://uknowledge.uky.edu/internalmedicine_facpub/83