title: Evidence for the involvement of sphingosine-1-phosphate in the homing and engraftment of hematopoietic stem cells to bone marrow.
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 (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.
authors: Stem Cell Institute at James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA.
authors: Mateusz
authors: M
authors: Adamiak
authors: Stem Cell Institute at James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA.
authors: Sylwia
authors: S
authors: Borkowska
authors: Institute of Molecular Cardiology, University of Louisville, Louisville, KY, USA.
authors: Marcin
authors: M
authors: Wysoczynski
authors: Stem Cell Institute at James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA.
authors: Malwina
authors: M
authors: Suszynska
authors: Stem Cell Institute at James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA.|Department of Regenerative Medicine, Medical University of Warsaw, Warsaw, Poland.
authors: Magda
authors: M
authors: Kucia
authors: Institute of Molecular Cardiology, University of Louisville, Louisville, KY, USA.
authors: Gregg
authors: G
authors: Rokosh
authors: Division of Cardiovascular Medicine, Gill Heart Institute, University of Kentucky, Lexington, KY, USA.
authors: Ahmed
authors: A
authors: Abdel-Latif
authors: Stem Cell Institute at James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA.
authors: Janina
authors: J
authors: Ratajczak
authors: Stem Cell Institute at James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA.|Department of Regenerative Medicine, Medical University of Warsaw, Warsaw, Poland.
authors: Mariusz Z
authors: MZ
authors: Ratajczak
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism*; D054377:Chemokine CXCL12 / Q000378:metabolism; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D008246:Lysophospholipids / Q000378:metabolism*; D008297:Male; D051379:Mice; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism; D055153:Stem Cell Niche / Q000502:physiology; D019172:Transplantation Conditioning / Q000379:methods*; D000099157:Sphingosine Kinase
chemical_list: D054377:Chemokine CXCL12; D008246:Lysophospholipids; D017853:Phosphotransferases (Alcohol Group Acceptor); D019718:Receptors, CXCR4; D013110:Sphingosine; D000099157:Sphingosine Kinase; C514936:CXCR4 protein, mouse; C515256:Cxcl12 protein, mouse; C060506:sphingosine 1-phosphate
keywords: CXCR4; Pathology Section; S1P; SDF-1; hematopoietic stem cells; stem cell homing