CXCR4 blockade and sphingosine-1-phosphate activation facilitate engraftment of haematopoietic stem and progenitor cells in a non-myeloablative transplant model

Br J Haematol. 2014 Feb;164(3):409-13. doi: 10.1111/bjh.12641. Epub 2013 Nov 3.

Abstract

Both immunosuppressive and cytoreductive effects of γ-irradiation contribute to engraftment of allogeneic haematopoietic stem and progenitor cells. We hypothesized that a release of host stem and progenitor cells from the niche prior to conditioning would permit engraftment after less intensive conditioning. Administration of AMD3100 and SEW2871 on days -4 to -2 followed by irradiation on day -1 in a non-myeloablative zebrafish transplant model resulted in a reduced radiation minimum dose of 10 Gy from 15 Gy being sufficient for engraftment. Targeting the SDF-1 (CXCL12)/CXCR4- and S1P/S1P1 -axis increased the efficacy of allografting in an experimental transplant model.

Keywords: AMD3100; SEW2871; conditioning; engraftment; zebrafish.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animal Experimentation
  • Animals
  • Benzylamines
  • Cyclams
  • Hematopoietic Stem Cell Transplantation / methods*
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / drug effects*
  • Heterocyclic Compounds / pharmacology*
  • Lysophospholipids / genetics
  • Lysophospholipids / metabolism*
  • Oxadiazoles / pharmacology*
  • Receptors, CXCR4 / antagonists & inhibitors*
  • Receptors, CXCR4 / genetics
  • Receptors, CXCR4 / metabolism
  • Signal Transduction
  • Sphingosine / analogs & derivatives*
  • Sphingosine / genetics
  • Sphingosine / metabolism
  • Thiophenes / pharmacology*
  • Transplantation Chimera
  • Transplantation, Homologous
  • Zebrafish

Substances

  • Benzylamines
  • Cyclams
  • Heterocyclic Compounds
  • Lysophospholipids
  • Oxadiazoles
  • Receptors, CXCR4
  • SEW2871
  • Thiophenes
  • sphingosine 1-phosphate
  • Sphingosine
  • plerixafor