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Blood, 1 April 2008, Vol. 111, No. 7, pp. 3415-3423. Prepublished online as a Blood First Edition Paper on January 17, 2008; DOI 10.1182/blood-2007-11-122119. This Article Full Text (PDF) All Versions of this Article: blood-2007-11-122119v1 111/7/3415    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 Zhang, C. C. Articles by Lodish, H. F Search for Related Content PubMed PubMed Citation Articles by Zhang, C. C. Articles by Lodish, H. F Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted November 5, 2007 Accepted January 16, 2008 Angiopoietin-like 5 and IGFBP2 stimulate ex vivo expansion of human cord blood hematopoietic stem cells as assayed by NOD/SCID transplantation Cheng Cheng Zhang*, Megan Kaba, Satoru Iizuka, HoangDinh Huynh, and Harvey F Lodish Whitehead Institute for Biomedical Research, Cambridge, MA Departments of Physiology and Developmental Biology, University of Texas Southwestern Medical Center, Dallas, TX Department of Biology, Massachusetts Institute of Technology, Cambridge, MA * Corresponding author; email: alec.zhang{at}utsouthwestern.edu. Pluripotent hematopoietic stem cells (HSCs) are the basis of bone marrow transplantation and are attractive target cells for hematopoietic gene therapy, but these important clinical applications have been severely hampered by difficulties in ex vivo expansion of HSCs. In particular, the use of cord blood for adult transplantation is greatly limited by the number of HSCs. Previously we identified Angiopoietin-like proteins and IGF binding protein 2 (IGFBP2) as new hormones that, together with other factors, can expand mouse bone marrow HSCs in culture. Here we measure the activity of multipotent human SCID-repopulating cells (SRCs) by transplantation into the nonobese diabetic severe combined immunodeficiency (NOD/SCID) mice; secondary transplantation was performed to evaluate the self-renewal potential of SRCs. A serum- free medium containing SCF, TPO, and FGF-1 or Flt3-L cannot significantly support expansion of the SRCs present in human cord blood CD133+ cells. Addition of either Angiopoietin-like 5, or IGF binding protein 2 to the cultures led to a sizable expansion of HSC numbers, as assayed by NOD/SCID transplantation. A serum-free culture containing SCF, TPO, FGF-1, Angiopoietin-like 5, and IGFBP2 supports a ~20 fold net expansion of repopulating human cord blood HSCs, a number potentially applicable to several clinical processes including HSC transplantation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. Zhao, T. I. Pestina, M. Nasimuzzaman, P. Mehta, P. W. Hargrove, and D. A. Persons Amelioration of murine {beta}-thalassemia through drug selection of hematopoietic stem cells transduced with a lentiviral vector encoding both {gamma}-globin and the MGMT drug-resistance gene Blood, June 4, 2009; 113(23): 5747 - 5756. [Abstract] [Full Text] [PDF] D. L. Kleinberg, T. L. Wood, P. A. Furth, and A. V. Lee Growth Hormone and Insulin-Like Growth Factor-I in the Transition from Normal Mammary Development to Preneoplastic Mammary Lesions Endocr. Rev., February 1, 2009; 30(1): 51 - 74. [Abstract] [Full Text] [PDF]

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