title: CXCR4 blockade and sphingosine-1-phosphate activation facilitate engraftment of haematopoietic stem and progenitor cells in a non-myeloablative transplant model.
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.
authors.affiliation: Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus der Technischen Universität, Dresden, Germany.
authors.forename: Nona
authors.initials: N
authors.lastname: Shayegi
authors.forename: Claudia
authors.initials: C
authors.lastname: Meyer
authors.forename: Katrin
authors.initials: K
authors.lastname: Lambert
authors.forename: Gerhard
authors.initials: G
authors.lastname: Ehninger
authors.forename: Michael
authors.initials: M
authors.lastname: Brand
authors.forename: Martin
authors.initials: M
authors.lastname: Bornhäuser
mesh_terms: D032761:Animal Experimentation; D000818:Animals; D001596:Benzylamines; D000080027:Cyclams; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects*; D006571:Heterocyclic Compounds / Q000494:pharmacology*; D008246:Lysophospholipids / Q000235:genetics / Q000378:metabolism*; D010069:Oxadiazoles / Q000494:pharmacology*; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000235:genetics / Q000378:metabolism; D013876:Thiophenes / Q000494:pharmacology*; D018183:Transplantation Chimera; D014184:Transplantation, Homologous; D015027:Zebrafish
chemical_list: D001596:Benzylamines; D000080027:Cyclams; D006571:Heterocyclic Compounds; D008246:Lysophospholipids; D010069:Oxadiazoles; D019718:Receptors, CXCR4; C503964:SEW2871; D013876:Thiophenes; C060506:sphingosine 1-phosphate; D013110:Sphingosine; C088327:plerixafor
keywords: AMD3100; SEW2871; conditioning; engraftment; zebrafish