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 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 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 Stier, S. Articles by Scadden, D. T. Search for Related Content PubMed PubMed Citation Articles by Stier, S. Articles by Scadden, D. T. Related Collections Hematopoiesis and Stem Cells Cell Cycle Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 August 2003, Vol. 102, No. 4, pp. 1260-1266 HEMATOPOIESIS 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 From the Center for Regenerative Medicine and Technology, AIDS Research Center and Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA. 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. Since p21 was necessary to maintain stem cell quiescence and its absence sufficient to permit increased murine stem cell cycling, we tested whether reduction of p21 alone in human 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. Further, we demonstrate full multilineage reconstitution capability in cells where p21 expression was knocked down. Therefore, lifting the brake on cell proliferation by altering cell cycle checkpoints provides an alternative paradigm for increasing hematopoietic stem cell numbers. This approach may be useful 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] N. Miyake, A. C.M. Brun, M. Magnusson, K. Miyake, D. T. Scadden, and S. Karlsson HOXB4-Induced Self-Renewal of Hematopoietic Stem Cells Is Significantly Enhanced by p21 Deficiency Stem Cells, March 1, 2006; 24(3): 653 - 661. [Abstract] [Full Text] [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] B. Faiola, E. S. Fuller, V. A. Wong, L. Pluta, D. J. Abernethy, J. Rose, and L. Recio Exposure of Hematopoietic Stem Cells to Benzene or 1,4-Benzoquinone Induces Gender-Specific Gene Expression Stem Cells, September 1, 2004; 22(5): 750 - 758. [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