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Prepublished online as a Blood First Edition Paper on October 24, 2002; DOI 10.1182/blood-2002-07-2254. This Article Full Text 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 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 Senju, S. Articles by Nishimura, Y. Search for Related Content PubMed PubMed Citation Articles by Senju, S. Articles by Nishimura, Y. Related Collections Hematopoiesis and Stem Cells Immunobiology Immunotherapy Gene Therapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 May 2003, Vol. 101, No. 9, pp. 3501-3508 IMMUNOBIOLOGY 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 From the Division of Immunogenetics, Department of Neuroscience and Immunology, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan; and the Division of Developmental Genetics, Department of Organogenesis, Institute of Molecular Embryology and Genetics, Kumamoto University, Japan. 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 bacteriologic Petri dishes without feeder cells and further cultured. In about 7 days, irregularly shaped floating cells with protrusions appeared and these expressed major histocompatibility complex 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 (ES cell-derived dendritic cells), and the functions of ES-DCs were comparable with those of DCs generated from bone marrow cells. Upon transfer to new dishes and stimulation with interleukin-4 plus tumor necrosis factor , combined with anti-CD40 monoclonal antibody or lipopolysaccharide, 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 pigeon cytochrome C epitope presented the epitope efficiently in the context of Ek. We primed ovalbumin (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 immunomodulation therapy and gene-trap investigations of DCs. © 2003 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Senju, M. Haruta, Y. Matsunaga, S. Fukushima, T. Ikeda, K. Takahashi, K. Okita, S. Yamanaka, and Y. Nishimura Characterization of Dendritic Cells and Macrophages Generated by Directed Differentiation from Mouse Induced Pluripotent Stem Cells Stem Cells, May 1, 2009; 27(5): 1021 - 1031. [Abstract] [Full Text] [PDF] K.-D. Choi, J. Yu, K. Smuga-Otto, G. Salvagiotto, W. Rehrauer, M. Vodyanik, J. Thomson, and I. Slukvin Hematopoietic and Endothelial Differentiation of Human Induced Pluripotent Stem Cells Stem Cells, March 1, 2009; 27(3): 559 - 567. [Abstract] [Full Text] [PDF] S. Senju, H. Suemori, H. Zembutsu, Y. Uemura, S. Hirata, D. Fukuma, H. Matsuyoshi, M. Shimomura, M. Haruta, S. Fukushima, et al. Genetically Manipulated Human Embryonic Stem Cell-Derived Dendritic Cells with Immune Regulatory Function Stem Cells, November 1, 2007; 25(11): 2720 - 2729. [Abstract] [Full Text] [PDF] T. Okazaki and T. Honjo PD-1 and PD-1 ligands: from discovery to clinical application Int. Immunol., July 2, 2007; (2007) dxm057v1. [Abstract] [Full Text] [PDF] S. Hirata, H. Matsuyoshi, D. Fukuma, A. Kurisaki, Y. Uemura, Y. Nishimura, and S. Senju Involvement of Regulatory T Cells in the Experimental Autoimmune Encephalomyelitis-Preventive Effect of Dendritic Cells Expressing Myelin Oligodendrocyte Glycoprotein plus TRAIL J. Immunol., January 15, 2007; 178(2): 918 - 925. [Abstract] [Full Text] [PDF] H. Komori, T. Nakatsura, S. Senju, Y. Yoshitake, Y. Motomura, Y. Ikuta, D. Fukuma, K. Yokomine, M. Harao, T. Beppu, et al. Identification of HLA-A2- or HLA-A24-Restricted CTL Epitopes Possibly Useful for Glypican-3-Specific Immunotherapy of Hepatocellular Carcinoma. Clin. Cancer Res., May 1, 2006; 12(9): 2689 - 2697. [Abstract] [Full Text] [PDF] I. I. Slukvin, M. A. Vodyanik, J. A. Thomson, M. E. Gumenyuk, and K.-D. Choi Directed Differentiation of Human Embryonic Stem Cells into Functional Dendritic Cells through the Myeloid Pathway. J. Immunol., March 1, 2006; 176(5): 2924 - 2932. [Abstract] [Full Text] [PDF] Y. Motomura, S. Senju, T. Nakatsura, H. Matsuyoshi, S. Hirata, M. Monji, H. Komori, D. Fukuma, H. Baba, and Y. Nishimura Embryonic Stem Cell-Derived Dendritic Cells Expressing Glypican-3, a Recently Identified Oncofetal Antigen, Induce Protective Immunity against Highly Metastatic Mouse Melanoma, B16-F10 Cancer Res., February 15, 2006; 66(4): 2414 - 2422. [Abstract] [Full Text] [PDF] A. L. Olsen, D. L. Stachura, and M. J. Weiss Designer blood: creating hematopoietic lineages from embryonic stem cells Blood, February 15, 2006; 107(4): 1265 - 1275. [Abstract] [Full Text] [PDF] S. Hirata, S. Senju, H. Matsuyoshi, D. Fukuma, Y. Uemura, and Y. Nishimura Prevention of Experimental Autoimmune Encephalomyelitis by Transfer of Embryonic Stem Cell-Derived Dendritic Cells Expressing Myelin Oligodendrocyte Glycoprotein Peptide along with TRAIL or Programmed Death-1 Ligand J. Immunol., February 15, 2005; 174(4): 1888 - 1897. [Abstract] [Full Text] [PDF] M. M. Dikov, J. E. Ohm, N. Ray, E. E. Tchekneva, J. Burlison, D. Moghanaki, S. Nadaf, and D. P. Carbone Differential Roles of Vascular Endothelial Growth Factor Receptors 1 and 2 in Dendritic Cell Differentiation J. Immunol., January 1, 2005; 174(1): 215 - 222. [Abstract] [Full Text] [PDF] H. Matsuyoshi, S. Senju, S. Hirata, Y. Yoshitake, Y. Uemura, and Y. Nishimura Enhanced Priming of Antigen-Specific CTLs In Vivo by Embryonic Stem Cell-Derived Dendritic Cells Expressing Chemokine Along with Antigenic Protein: Application to Antitumor Vaccination J. Immunol., January 15, 2004; 172(2): 776 - 786. [Abstract] [Full Text] [PDF]

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