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Prepublished online as a Blood First Edition Paper on October 24, 2002October 24, 2002; DOI 10.1182/blood-2002-07-2254. This Article Full Text (PDF) All Versions of this Article: 2002-07-2254v1 2002-07-2254v2 101/9/3501    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 Senju, S. Articles by Nishimura, Y. Search for Related Content PubMed PubMed Citation Articles by Senju, S. Articles by Nishimura, Y. Social Bookmarking                   What's this? Submitted July 26, 2002 Accepted October 1, 2002 Generation and genetic modification of dendritic cells derived from mouse embryonic stem cells Satoru Senju, Shinya Hirata, Hidetake Matsuyoshi, Masako Masuda, Yasushi Uemura, Kimi Araki, Ken-ichi Yamamura, and Yasuharu Nishimura* Department of Neuroscience and Immunology, Division of Immunogenetics, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan Department of Organogenesis, Division of Developmental Genetics, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan * Corresponding author; email: mxnishim{at}gpo.kumamoto-u.ac.jp. We developed a method to generate dendritic cells (DCs) from mouse embryonic stem (ES) cells. We cultured ES cells for 10 days on feeder cell layers of OP9 in the presence of granulocyte macrophage colony stimulating factor in the latter 5 days. The resultant ES cell-derived cells were transferred to bacteriological Petri dishes without feeder cells and further cultured. In about 7 days, irregularly shaped floating cells with protrusions appeared and these expressed MHC class II, CD11c, CD80, and CD86, with the capacity to stimulate primary mixed lymphocyte reaction (MLR) and to process and present protein antigen to T cells. We designated them ES-DCs, and the functions of ES-DCs were comparable to those of DCs generated from bone marrow cells. Upon transfer to new dishes and stimulation with IL-4 plus TNF-, combined with anti-CD40 mAb or LPS, ES-DCs completely became mature DCs, characterized by a typical morphology and higher capacity to stimulate MLR. Using an expression vector containing the internal ribosomal entry site-puromycin N-acetyltransferase gene or a Cre-lox-mediated exchangeable gene-trap system, we could efficiently generate ES cell transfectants expressing the products of introduced genes after their differentiation to DCs. ES-DCs expressing invariant chain-fused to a PCC epitope presented the epitope efficiently in the context of Ek. We primed OVA-specific cytotoxic T lymphocytes in vivo by injecting mice with ES-DCs expressing OVA, thus demonstrating immunization with ES-DCs genetically engineered to express antigenic protein. The methods may be applicable to immuno-modulation therapy and gene-trap investigations of DCs. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Y. Matsunaga, D. Fukuma, S. Hirata, S. Fukushima, M. Haruta, T. Ikeda, I. Negishi, Y. Nishimura, and S. 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