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EMBRYONIC STEM CELLS

Genetically Manipulated Human Embryonic Stem Cell-Derived Dendritic Cells with Immune Regulatory Function

^aDepartment of Immunogenetics, Graduate School of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan;
^bLaboratory of Embryonic Stem Cell Research, Stem Cell Research Center, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan;
^cLaboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan;
^dDepartment of Development and Differentiation, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan

Key Words. Dendritic cells • Embryonic stem cells • Cell differentiation • Cell therapy

Correspondence: Satoru Senju, M.D., Ph.D., Department of Immunogenetics, Graduate School of Medical and Pharmaceutical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan. Telephone: 81-96-373-5313; Fax: 81-96-373-5314; e-mail: senjusat{at}gpo.kumamoto-u.ac.jp

Received April 30, 2007; accepted for publication July 27, 2007.
First published online in STEM CELLS EXPRESS   August 9, 2007.



Genetically manipulated dendritic cells (DC) are considered to be a promising means for antigen-specific immune therapy. This study reports the generation, characterization, and genetic modification of DC derived from human embryonic stem (ES) cells. The human ES cell-derived DC (ES-DC) expressed surface molecules typically expressed by DC and had the capacities to stimulate allogeneic T lymphocytes and to process and present protein antigen in the context of histocompatibility leukocyte antigen (HLA) class II molecule. Genetic modification of human ES-DC can be accomplished without the use of viral vectors, by the introduction of expression vector plasmids into undifferentiated ES cells by electroporation and subsequent induction of differentiation of the transfectant ES cell clones to ES-DC. ES-DC introduced with invariant chain-based antigen-presenting vectors by this procedure stimulated HLA-DR-restricted antigen-specific T cells in the absence of exogenous antigen. Forced expression of programmed death-1-ligand-1 in ES-DC resulted in the reduction of the proliferative response of allogeneic T cells cocultured with the ES-DC. Generation and genetic modification of ES-DC from nonhuman primate (cynomolgus monkey) ES cells was also achieved by the currently established method. ES-DC technology is therefore considered to be a novel means for immune therapy.

Disclosure of potential conflicts of interest is found at the end of this article.