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Blood, 1 March 2006, Vol. 107, No. 5, pp. 2162-2169. Prepublished online as a Blood First Edition Paper on November 3, 2005; DOI 10.1182/blood-2005-06-2284. This Article Full Text (PDF) All Versions of this Article: 2005-06-2284v1 107/5/2162    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 Hess, D. A Articles by Nolta, J. A Search for Related Content PubMed PubMed Citation Articles by Hess, D. A Articles by Nolta, J. A Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 8, 2005 Accepted October 20, 2005 Selection based on CD133 and high aldehyde dehydrogenase activity isolates long-term reconstituting human hematopoietic stem cells David A Hess*, Louisa Wirthlin, Timothy P Craft, Phillip E Herrbrich, Sarah A Hohm, Ryan Lahey, William C Eades, Michael H Creer, and Jan A Nolta Department of Internal Medicine, Division of Oncology, Hematopoietic Development and Malignancy Group, Washington University School of Medicine, St. Louis, MO, USA Departments of Pathology and Laboratory Medicine, St. Louis University School of Medicine, St. Louis, MO, USA * Corresponding author; email: dhess{at}im.wustl.edu. The development of novel cell-based therapies requires understanding of distinct human hematopoietic stem and progenitor cell populations. We recently isolated reconstituting HSC by lineage depletion and purification based on high aldehyde dehydrogenase activity (ALDHhiLin- cells). Here, we further dissected the ALDHhiLin- population by selection for CD133, a surface molecule expressed on progenitors from hematopoietic, endothelial, and neural lineages. ALDHhiCD133+Lin- cells were primarily CD34+, but also included CD34-CD38-CD133+ cells, a phenotype previously associated with repopulating function. Both ALDHhiCD133-Lin- and ALDHhiCD133+Lin- cells demonstrated distinct clonogenic progenitor function in vitro, whereas only the ALDHhiCD133+Lin- population seeded the murine bone marrow 48 hours post-transplantation. Significant human cell repopulation was only observed in NOD/SCID and NOD/SCID 2M null mice transplanted with ALDHhiCD133+Lin- cells. Limiting dilution analysis demonstrated a 10-fold increase in the frequency of NOD/SCID repopulating cells compared to CD133+Lin- cells, suggesting that high ALDH activity further purified cells with repopulating function. Transplanted ALDHhiCD133+Lin- cells also maintained primitive hematopoietic phenotypes (CD34+CD38-), and demonstrated enhanced repopulating function in serially transplanted secondary recipients. Cell selection based on ALDH activity and CD133 expression provides a novel purification of HSC with long-term repopulating function, and may be considered an alternative to CD34 cell selection for stem cell therapies. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: B. J. Capoccia, D. L. Robson, K. D. Levac, D. J. Maxwell, S. A. Hohm, M. J. Neelamkavil, G. I. Bell, A. Xenocostas, D. C. Link, D. Piwnica-Worms, et al. 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