SEARCH:   Advanced

Prepublished online as a Blood First Edition Paper on April 17, 2003; DOI 10.1182/blood-2002-10-3053. This Article Full Text (PDF) All Versions of this Article: 2002-10-3053v1 102/4/1260    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 Stier, S. Articles by Scadden, D. T Search for Related Content PubMed PubMed Citation Articles by Stier, S. Articles by Scadden, D. T Social Bookmarking                   What's this? Submitted October 15, 2002 Accepted March 20, 2003 Ex vivo targeting of p21Cip1/Waf1 permits relative expansion of human hematopoietic stem cells Sebastian Stier, Tao Cheng, Randolf Forkert, Christoph Lutz, David M Dombkowski, Jie Lin Zhang, and David T Scadden* Center for Regenerative Medicine and Technology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA * Corresponding author; email: scadden.david{at}mgh.harvard.edu. Relative quiescence is a defining characteristic of hematopoietic stem cells. Reasoning that inhibitory tone dominates control of stem cell cycling, we previously showed that mice engineered to be deficient in the cyclin dependent kinase inhibitor, p21Cip1/Waf1 (p21), have an increased stem cell pool under homeostatic conditions. The effect of p21 appears to be independent of that of another stem cell inhibitor, TGF-. Since p21 was necessary to maintain stem cell quiescence and its absence sufficient to permit increased stem cell cycling, we tested whether reduction of p21 alone in adult derived stem cells could affect stem cell proliferation. We demonstrate here that interrupting p21 expression ex vivo resulted in expanded stem cell number and in vivo stem cell function compared with control, manipulated cells. Therefore, lifting the brake on cell proliferation by altering cell cycle checkpoints provides an alternative paradigm for increasing hematopoietic stem cell numbers that may be exploited for relative ex vivo human stem cell expansion. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: B. Li, N. Jia, D. L. Waning, F.-C. Yang, L. S. Haneline, and K. T. Chun Cul4A is required for hematopoietic stem-cell engraftment and self-renewal Blood, October 1, 2007; 110(7): 2704 - 2707. [Abstract] [Full Text] [PDF] H. Araki, K. Yoshinaga, P. Boccuni, Y. Zhao, R. Hoffman, and N. Mahmud Chromatin-modifying agents permit human hematopoietic stem cells to undergo multiple cell divisions while retaining their repopulating potential Blood, April 15, 2007; 109(8): 3570 - 3578. [Abstract] [Full Text] [PDF] M. Holtz, S. J. Forman, and R. Bhatia Growth Factor Stimulation Reduces Residual Quiescent Chronic Myelogenous Leukemia Progenitors Remaining after Imatinib Treatment Cancer Res., February 1, 2007; 67(3): 1113 - 1120. [Abstract] [Full Text] [PDF] U. Blank, G. Karlsson, J. L. Moody, T. Utsugisawa, M. Magnusson, S. Singbrant, J. Larsson, and S. Karlsson Smad7 promotes self-renewal of hematopoietic stem cells Blood, December 15, 2006; 108(13): 4246 - 4254. [Abstract] [Full Text] [PDF] J. L. Zhang, C. S. Crumpacker, and D. T. Scadden Primitive Hematopoietic Cells Resist HIV-1 Infection Via P21Waf1/Cip1/Sdi1. Blood (ASH Annual Meeting Abstracts), November 16, 2006; 108(11): 490 - 490. [Abstract] [PDF] H. Yu, Y. Yuan, H. Shen, and T. Cheng Hematopoietic stem cell exhaustion impacted by p18INK4C and p21Cip1/Waf1 in opposite manners Blood, February 1, 2006; 107(3): 1200 - 1206. [Abstract] [Full Text] [PDF] E. Passegue, A. J. Wagers, S. Giuriato, W. C. Anderson, and I. L. Weissman Global analysis of proliferation and cell cycle gene expression in the regulation of hematopoietic stem and progenitor cell fates J. Exp. Med., December 5, 2005; 202(11): 1599 - 1611. [Abstract] [Full Text] [PDF] A. Tripp, P. Banerjee, M. Sieburg, V. Planelles, F. Li, and G. Feuer Induction of Cell Cycle Arrest by Human T-Cell Lymphotropic Virus Type 1 Tax in Hematopoietic Progenitor (CD34+) Cells: Modulation of p21cip1/waf1 and p27kip1 Expression J. Virol., November 15, 2005; 79(22): 14069 - 14078. [Abstract] [Full Text] [PDF] F. Ishikawa, M. Yasukawa, B. Lyons, S. Yoshida, T. Miyamoto, G. Yoshimoto, T. Watanabe, K. Akashi, L. D. Shultz, and M. Harada Development of functional human blood and immune systems in NOD/SCID/IL2 receptor {gamma} chainnull mice Blood, September 1, 2005; 106(5): 1565 - 1573. [Abstract] [Full Text] [PDF] J. Qiu, Y. Takagi, J. Harada, N. Rodrigues, M. A. Moskowitz, D. T. Scadden, and T. Cheng Regenerative Response in Ischemic Brain Restricted by p21cip1/waf1 J. Exp. Med., April 5, 2004; 199(7): 937 - 945. [Abstract] [Full Text] [PDF]

	Copyright © 2003 by American Society of Hematology         Online ISSN: 1528-0020