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Blood, 15 April 2004, Vol. 103, No. 8, pp. 2981-2989. Prepublished online as a Blood First Edition Paper on January 15, 2004; DOI 10.1182/blood-2003-10-3611. This Article Full Text Full Text (PDF) Supplemental Videos All Versions of this Article: 2003-10-3611v1 103/8/2981    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Avigdor, A. Articles by Lapidot, T. Search for Related Content PubMed PubMed Citation Articles by Avigdor, A. Articles by Lapidot, T. Related Collections Hematopoiesis and Stem Cells Cell Adhesion and Motility Signal Transduction Chemokines, Cytokines, and Interleukins Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS CD44 and hyaluronic acid cooperate with SDF-1 in the trafficking of human CD34+ stem/progenitor cells to bone marrow Abraham Avigdor, Polina Goichberg, Shoham Shivtiel, Ayelet Dar, Amnon Peled, Sarit Samira, Orit Kollet, Rami Hershkoviz, Ronen Alon, Izhar Hardan, Herzl Ben-Hur, David Naor, Arnon Nagler, and Tsvee Lapidot From the Immunology Department, Weizmann Institute of Science, Rehovot, Israel; Hematology and Bone Marrow Transplantation Department, Chaim Sheba Medical Center, Tel-Hashomer, Israel; Gene Therapy Institute, Hadassah University Hospital, Jerusalem, Israel; Department of Internal Medicine, Assaf-Harofeh Medical Center, Zerifin, Israel; Laboratory of Experimental Medicine, Park Rabin, Rehovot, Israel; and the Lautenberg Center for General and Tumor Immunology, The Hebrew University-Hadassah Medical School, Jerusalem, Israel. Trafficking of human CD34+ stem/progenitor cells (HSCs/HPCs) is regulated by chemokines, cytokines, proteolytic enzymes, and adhesion molecules. We report that the adhesion receptor CD44 and its major ligand, hyaluronic acid (HA), are essential for homing into the bone marrow (BM) and spleen of nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice and engraftment by human HSCs. Homing was blocked by anti-CD44 monoclonal antibodies (mAbs) or by soluble HA, and it was significantly impaired after intravenous injection of hyaluronidase. Furthermore, stromal cell-derived factor-1 (SDF-1) was found to be a rapid and potent stimulator of progenitor adhesion to immobilized HA, leading to formation of actin-containing protrusions with CD44 located at their tips. HPCs migrating on HA toward a gradient of SDF-1 acquired spread and polarized morphology with CD44 concentrating at the pseudopodia at the leading edge. These morphologic alterations were not observed when the progenitors were first exposed to anti-CD44 mAbs, demonstrating a crosstalk between CD44 and CXCR4 signaling. Unexpectedly, we found that HA is expressed on human BM sinusoidal endothelium and endosteum, the regions where SDF-1 is also abundant. Taken together, our data suggest a key role for CD44 and HA in SDF-1–dependent transendothelial migration of HSCs/HPCs and their final anchorage within specific niches of the BM. (Blood. 2004;103:2981-2989) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: I. Stroo, G. Stokman, G. J. D. Teske, S. Florquin, and J. C. Leemans Haematopoietic stem cell migration to the ischemic damaged kidney is not altered by manipulating the SDF-1/CXCR4-axis Nephrol. Dial. Transplant., July 1, 2009; 24(7): 2082 - 2088. [Abstract] [Full Text] [PDF] B.-C. Lee, H.-C. Hsu, W.-Y. I. Tseng, C.-Y. Chen, H.-J. Lin, Y.-L. Ho, M.-J. 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