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

      British Journal of Haematology
      Animal Experimentation, Animals, Hematopoietic Stem Cell Transplantation, methods, Hematopoietic Stem Cells, cytology, drug effects, Heterocyclic Compounds, pharmacology, Lysophospholipids, genetics, metabolism, Oxadiazoles, Receptors, CXCR4, antagonists & inhibitors, Signal Transduction, Sphingosine, analogs & derivatives, Thiophenes, Transplantation Chimera, Transplantation, Homologous, Zebrafish

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          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. © 2013 John Wiley & Sons Ltd.

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