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Blood, 15 March 2008, Vol. 111, No. 6, pp. 2953-2961. Prepublished online as a Blood First Edition Paper on December 4, 2007; DOI 10.1182/blood-2007-10-117366. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-10-117366v1 111/6/2953    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 Chan, K.-M. Articles by Zavazava, N. Search for Related Content PubMed PubMed Citation Articles by Chan, K.-M. Articles by Zavazava, N. Related Collections Plenary Papers Stem Cells in Hematology Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PLENARY PAPER Hematopoiesis and immunity of HOXB4-transduced embryonic stem cell–derived hematopoietic progenitor cells Kun-Ming Chan1,2, Sabrina Bonde1, Hannes Klump3, and Nicholas Zavazava1,4 1 Department of Internal Medicine, University of Iowa and Veteran Affairs Medical Center, Iowa City; 2 Department of General Surgery, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan; 3 Department of Experimental Hematology, Hannover Medical School, Hannover, Germany; and 4 Immunology Graduate Program, University of Iowa, Iowa City The ability of embryonic stem (ES) cells to form cells and tissues from all 3 germ layers can be exploited to generate cells that can be used to treat diseases. In particular, successful generation of hematopoietic cells from ES cells could provide safer and less immunogenic cells than bone marrow cells, which require severe host preconditioning when transplanted across major histocompatibility complex barriers. Here, we exploited the self-renewal properties of ectopically expressed HOXB4, a homeobox transcription factor, to generate hematopoietic progenitor cells (HPCs) that successfully induce high-level mixed chimerism and long-term engraftment in recipient mice. The HPCs partially restored splenic architecture in Rag2–/––immunodeficient mice. In addition, HPC-derived newly generated T cells were able to mount a peptide-specific response to lymphocytic choriomeningitis virus and specifically secreted interleukin-2 and interferon- upon CD3 stimulation. In addition, HPC-derived antigen presenting cells in chimeric mice efficiently presented viral antigen to wild-type T cells. These results demonstrate for the first time that leukocytes derived from ES cells ectopically expressing HOXB4 are immunologically functional, opening up new opportunities for the use of ES cell–derived HPCs in the treatment of hematologic and immunologic diseases. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: An ES cell–derived immune system Michael Kyba Blood 2008 111: 2948-2949. [Full Text] [PDF] This article has been cited by other articles: W. B. Tabayoyong, J. G. Salas, S. Bonde, and N. Zavazava HOXB4-Transduced Embryonic Stem Cell-Derived Lin-c-kit+ and Lin-Sca-1+ Hematopoietic Progenitors Express H60 and Are Targeted by NK Cells J. Immunol., November 1, 2009; 183(9): 5449 - 5457. [Abstract] [Full Text] [PDF] D. S. Kaufman Toward clinical therapies using hematopoietic cells derived from human pluripotent stem cells Blood, October 22, 2009; 114(17): 3513 - 3523. [Abstract] [Full Text] [PDF] S. L. McKinney-Freeman, O. Naveiras, F. Yates, S. Loewer, M. Philitas, M. Curran, P. J. Park, and G. Q. Daley Surface antigen phenotypes of hematopoietic stem cells from embryos and murine embryonic stem cells Blood, July 9, 2009; 114(2): 268 - 278. [Abstract] [Full Text] [PDF]

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