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Blood, 15 April 2004, Vol. 103, No. 8, pp. 2942-2949. Prepublished online as a Blood First Edition Paper on December 24, 2003; DOI 10.1182/blood-2003-07-2607. This Article Full Text (PDF) All Versions of this Article: 2003-07-2607v1 103/8/2942    most recent Alert me when this article is cited Alert me if a correction is posted 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 Kahn, J. Articles by Lapidot, T. Search for Related Content PubMed PubMed Citation Articles by Kahn, J. Articles by Lapidot, T. Social Bookmarking                   What's this? Submitted July 31, 2003 Accepted December 11, 2003 Overexpression of CXCR4 on human CD34+ progenitors increases their proliferation, migration, and NOD/SCID repopulation Joy Kahn, Tamara Byk, Lottie Jansson-Sjostrand, Isabelle Petit, Shoham Shivtiel, Arnon Nagler, Izhar Hardan, Varda Deutsch, Zulma Gazit, Dan Gazit, Stefan Karlsson, and Tsvee Lapidot* Department of Immunology, Weizmann Institute of Science, Rehovot, Israel Department of Molecular Medicine and Gene Therapy, Lund University, Lund, Sweden Department of Bone Marrow Transplantation, Chaim Sheba Medical Center, Ramat Gan, Israel Hematology Institute, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel Skeletal Biotechnology Laboratory, Hebrew University, Hadassah Medical Center, Jerusalem, Israel * Corresponding author; email: Tsvee.Lapidot{at}weizmann.ac.il. A major limitation to clinical stem cell mediated gene therapy protocols is the low levels of engraftment by transduced progenitors. We report that CXCR4 overexpression on human CD34+ progenitors utilizing a lentiviral gene transfer technique helped navigate these cells to the murine BM and spleen in response to SDF-1 signaling. CXCR4 overexpressing cells exhibited significant increases in SDF-1 mediated chemotaxis and actin polymerization compared to control cells. A major advantage of CXCR4 overexpression was demonstrated by the ability of transduced CD34+ cells to respond to lower, physiological levels of SDF-1 when compared to control cells, leading to improved SDF-1 induced migration, proliferation/survival, and finally resulting in significantly higher levels of in vivo repopulation of NOD/SCID mice including primitive CD34+/CD38-/low cells. Importantly, no cellular transformation was observed following transduction with the CXCR4 vector. Unexpectedly, we documented lack of receptor internalization in response to high levels of SDF-1, which can also contribute to increased migration and proliferation by the transduced CD34+ cells. Our results suggest CXCR4 overexpression for improved definitive human stem cell motility, retention and multi-lineage repopulation, which could be beneficial for in vivo navigation and expansion of hematopoietic progenitors. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: F. H. Seeger, T. Rasper, M. Koyanagi, H. Fox, A. M. Zeiher, and S. Dimmeler CXCR4 Expression Determines Functional Activity of Bone Marrow-Derived Mononuclear Cells for Therapeutic Neovascularization in Acute Ischemia Arterioscler Thromb Vasc Biol, November 1, 2009; 29(11): 1802 - 1809. [Abstract] [Full Text] [PDF] V. Enzmann, E. Yolcu, H. J. Kaplan, and S. T. 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