title: Dextran sulfate and stromal cell derived factor-1 promote CXCR4 expression and improve bone marrow homing efficiency of infused hematopoietic stem cells.
abstract: Although the homing of hematopoietic stem cells (HSC) to the bone marrow (BM) is a crucial step in hematopoietic development and BM repopulation, the mechanisms underlying these processes have not been fully clarified. Recent studies suggest that interaction between the chemokine receptor CXCR4 and its ligand, stromal cell-derived factor 1 (SDF-1), plays a critical role in these processes. In addition, dextran sulfate increases plasma SDF-1 levels in mice and nonhuman primates. Thus, we examined the effects of preconditioning with SDF-1 and dextran sulfate on the homing efficiency of HSCs following BM transplantation in mice. We found that the preconditioning of donor mice with either SDF-1 or dextran sulfate enhanced the homing efficiency of infused HSCs in vivo. The greatest effects were obtained with dextran sulfate. Moreover, reverse transcriptase polymerase chain reaction analysis demonstrated that SDF-1 and dextran sulfate increased transcription of a variety of homing-related genes, including those for CXCR4, lymphocyte function associated antigen-1, matrix metalloproteinase-9, very late antigen-4/5, and macrophage inflammatory protein-1. We suggest that whereas SDF-1 directly acts to upregulate CXCR4 expression in HSCs, dextran sulfate acts via multiple pathways involved in the induction of various homing-related molecules, in addition to SDF-1. Thus, preconditioning donors with dextran sulfate offers a novel clinical approach for improving the homing and engraftment of HSCs in the BM.
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Hayakawa
authors.forename: Makoto
authors.initials: M
authors.lastname: Migita
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ueda
authors.forename: Ryuji
authors.initials: R
authors.lastname: Fukazawa
authors.forename: Kumi
authors.initials: K
authors.lastname: Adachi
authors.forename: Yuki
authors.initials: Y
authors.lastname: Ooue
authors.forename: Mari
authors.initials: M
authors.lastname: Hayakawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Shimada
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Fukunaga
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000187:drug effects* / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects* / Q000235:genetics; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000378:metabolism*; D016264:Dextran Sulfate / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014916:Whole-Body Irradiation
chemical_list: C514936:CXCR4 protein, mouse; D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D019718:Receptors, CXCR4; D011994:Recombinant Proteins; D049452:Green Fluorescent Proteins; D016264:Dextran Sulfate