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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.

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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–/–{gamma}Formula–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-{gamma} 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.


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Related Article in Blood Online:

An ES cell–derived immune system
Michael Kyba
Blood 2008 111: 2948-2949. [Full Text] [PDF]





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