Research Papers: Pathology:

Evidence for the involvement of sphingosine-1-phosphate in the homing and engraftment of hematopoietic stem cells to bone marrow

Mateusz Adamiak, Sylwia Borkowska, Marcin Wysoczynski, Malwina Suszynska, Magda Kucia, Gregg Rokosh, Ahmed Abdel-Latif, Janina Ratajczak and Mariusz Z. Ratajczak _

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Oncotarget. 2015; 6:18819-18828. https://doi.org/10.18632/oncotarget.4710

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Mateusz Adamiak1, Sylwia Borkowska1, Marcin Wysoczynski2, Malwina Suszynska1, Magda Kucia1,3, Gregg Rokosh2, Ahmed Abdel-Latif4, Janina Ratajczak1, Mariusz Z. Ratajczak1,3

1Stem Cell Institute at James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA

2Institute of Molecular Cardiology, University of Louisville, Louisville, KY, USA

3Department of Regenerative Medicine, Medical University of Warsaw, Warsaw, Poland

4Division of Cardiovascular Medicine, Gill Heart Institute, University of Kentucky, Lexington, KY, USA

Correspondence to:

Mariusz Z. Ratajczak, e-mail: [email protected]

Keywords: Pathology Section, S1P, SDF-1, CXCR4, stem cell homing, hematopoietic stem cells

Received: June 09, 2015     Accepted: July 07, 2015     Published: July 17, 2015


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 (CXCR4fl/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.

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