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Blood, 15 March 2004, Vol. 103, No. 6, pp. 2079-2087. Prepublished online as a Blood First Edition Paper on November 20, 2003; DOI 10.1182/blood-2003-06-1770. This Article Full Text (PDF) All Versions of this Article: 2003-06-1770v1 103/6/2079    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 Ahmed, F. Articles by Yong, K. L Search for Related Content PubMed PubMed Citation Articles by Ahmed, F. Articles by Yong, K. L Social Bookmarking                   What's this? Submitted June 2, 2003 Accepted November 12, 2003 Impaired bone marrow homing of cytokine activated CD34+ cells in the NOD/SCID model Forhad Ahmed, Stuart J Ings, Arnold R Pizzey, Michael P Blundell, Adrian J Thrasher, Hong T Ye, Anne Fahey, David C Linch, and Kwee L Yong* Department of Haematology, Royal Free and University College Medical School, London, United Kingdom Department of Histopathology, Royal Free and University College Medical School, London, United Kingdom Molecular Immunology Unit, Insitute of Child Health, London, United Kingdom Department of Pathology, Guangxi Medical University, Guangxi, China * Corresponding author; email: kwee.yong{at}ucl.ac.uk. Reduced engraftment potential of haemopoietic stem/progenitor cells (HSPC) following exposure to cytokines may be related to impaired homing ability of actively cycling cells. We tested this hypothesis by quantifying the short term homing of human adult CD34+ cells in NOD/SCID animals. We show that the loss of engraftment ability of cytokine activated CD34+ cells is associated with a reduction in homing of CFC to BM at 24hr post-transplantation (from median 2.8% (range 1.9-6.1) to 0.3 (0.0-0.7), n=3, P<0.01) coincident with an increase in CFC accumulation in the lungs (P<0.01). Impaired BM homing of cytokine activated cells was not restored by using sorted cells in G0G1, nor by inducing cell cycle arrest at the G1/S border. Blocking Fas ligation in vivo did not increase the BM homing of cultured cells. Finally we tested cytokine combinations or culture conditions previously reported to restore the engraftment of cultured cells but did not find that any of these was able to reverse the changes in homing behaviour of cytokine-exposed cells. We suggest that these changes in homing, and, as a consequence, engraftment, are due to increased migratory capacity of infused activated cells, leading to loss of selectivity of the homing process. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: X. Wang, W. Zhang, T. Ishii, S. Sozer, J. Wang, M. Xu, and R. Hoffman Correction of the Abnormal Trafficking of Primary Myelofibrosis CD34+ Cells by Treatment with Chromatin-Modifying Agents Cancer Res., October 1, 2009; 69(19): 7612 - 7618. [Abstract] [Full Text] [PDF] X. Zhang and Q. Pang Response: Homing defect in hematopoietic cells from Fanconi anemia patients Blood, May 21, 2009; 113(21): 5362 - 5362. [Full Text] [PDF] J. Foguenne, I. Di Stefano, O. Giet, Y. Beguin, and A. Gothot Ex vivo expansion of hematopoietic progenitor cells is associated with downregulation of {alpha}4 integrin- and CXCR4-mediated engraftment in NOD/SCID {beta}2-microglobulin-null mice Haematologica, February 1, 2009; 94(2): 185 - 194. [Abstract] [Full Text] [PDF] F. R. Santoni de Sio, P. Cascio, A. Zingale, M. Gasparini, and L. Naldini Proteasome activity restricts lentiviral gene transfer into hematopoietic stem cells and is down-regulated by cytokines that enhance transduction Blood, June 1, 2006; 107(11): 4257 - 4265. [Abstract] [Full Text] [PDF]

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