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Related Collections Transplantation Chemokines, Cytokines, and Interleukins Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 May 2001, Vol. 97, No. 10, pp. 3283-3291 TRANSPLANTATION Rapid and efficient homing of human CD34+CD38/lowCXCR4+ stem and progenitor cells to the bone marrow and spleen of NOD/SCID and NOD/SCID/B2mnull mice Orit Kollet, Asaf Spiegel, Amnon Peled, Isabelle Petit, Tamara Byk, Rami Hershkoviz, Esther Guetta, Gad Barkai, Arnon Nagler, and Tsvee Lapidot From the Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel; Department of Internal Medicine, Meir Hospital, Kfar Saba, Israel; Department of Obstetrics and Gynecology and Danek Gertner Institute of Human Genetics, Sheba Medical Center Tel-Hashomer, and Department of Human Genetics and Molecular Medicine, Sackler Faculty of Medicine, Tel-Aviv University, Ramat-Aviv, Tel-Aviv, Israel; and Hadassah University Hospital, Jerusalem, Israel. Stem cell homing into the bone microenvironment is the first step in the initiation of marrow-derived blood cells. It is reported that human severe combined immunodeficient (SCID) repopulating cells home and accumulate rapidly, within a few hours, in the bone marrow and spleen of immunodeficient mice previously conditioned with total body irradiation. Primitive CD34+CD38/lowCXCR4+ cells capable of engrafting primary and secondary recipient mice selectively homed to the bone marrow and spleen, whereas CD34CD38/lowLin cells were not detected. Moreover, whereas freshly isolated CD34+CD38+/high cells did not home, in vivo stimulation with granulocyte colony-stimulating factor as part of the mobilization process, or in vitro stem cell factor stimulation for 2 to 4 days, potentiated the homing capabilities of cytokine-stimulated CD34+CD38+ cells. Homing of enriched human CD34+ cells was inhibited by pretreatment with anti-CXCR4 antibodies. Moreover, primitive CD34+CD38/lowCXCR4+ cells also homed in response to a gradient of human stromal cell-derived factor 1 (SDF-1), directly injected into the bone marrow or spleen of nonirradiated NOD/SCID mice. Homing was also inhibited by pretreatment of CD34+ cells with antibodies for the major integrins VLA-4, VLA-5, and LFA-1. Pertussis toxin, an inhibitor of signals mediated by Gi proteins, inhibited SDF-1-mediated in vitro transwell migration but not adhesion or in vivo homing of CD34+ cells. Homing of human CD34+ cells was also blocked by chelerythrine chloride, a broad-range protein kinase C inhibitor. This study reveals rapid and efficient homing to the murine bone marrow by primitive human CD34+CD38/lowCXCR4+ cells that is integrin mediated and depends on activation of the protein kinase C signal transduction pathway by SDF-1. © 2001 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? 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