title: Generation of mouse pluripotent stem cell-derived proliferating myeloid cells as an unlimited source of functional antigen-presenting cells.
abstract: The use of dendritic cells (DC) to prime tumor-associated antigen-specific T-cell responses provides a promising approach to cancer immunotherapy. Embryonic stem cells (ESC) and induced pluripotent stem cells (iPSC) can differentiate into functional DCs, thus providing an unlimited source of DCs. However, the previously established methods of generating practical volumes of DCs from pluripotent stem cells (PSC) require a large number of PSCs at the start of the differentiation culture. In this study, we generated mouse proliferating myeloid cells (pMC) as a source of antigen-presenting cells (APC) using lentivirus-mediated transduction of the c-Myc gene into mouse PSC-derived myeloid cells. The pMCs could propagate almost indefinitely in a cytokine-dependent manner, while retaining their potential to differentiate into functional APCs. After treatment with IL4 plus GM-CSF, the pMCs showed impaired proliferation and differentiated into immature DC-like cells (pMC-DC) expressing low levels of major histocompatibility complex (MHC)-I, MHC-II, CD40, CD80, and CD86. In addition, exposure to maturation stimuli induced the production of TNFα and IL12p70, and enhanced the expression of MHC-II, CD40, and CD86, which is thus suggestive of typical DC maturation. Similar to bone marrow-derived DCs, they stimulated a primary mixed lymphocyte reaction. Furthermore, the in vivo transfer of pMC-DCs pulsed with H-2K(b)-restricted OVA257-264 peptide primed OVA-specific cytotoxic T cells and elicited protection in mice against challenge with OVA-expressing melanoma. Overall, myeloid cells exhibiting cytokine-dependent proliferation and DC-like differentiation may be used to address issues associated with the preparation of DCs.
authors: Division of Immunology, Aichi Cancer Center Research Institute, Nagoya, Japan.
authors: Rong
authors: R
authors: Zhang
authors: Division of Immunology, Aichi Cancer Center Research Institute, Nagoya, Japan. Key Laboratory of Cancer Center, Chinese PLA General Hospital, Beijing, China.
authors: Tian-Yi
authors: TY
authors: Liu
authors: Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan. CREST, Japan Science and Technology Agency (JST), Kawaguchi, Saitama, Japan. yuemura@east.ncc.go.jp senjusat@gpo.kumamoto-u.ac.jp.
authors: Satoru
authors: S
authors: Senju
authors: Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan. CREST, Japan Science and Technology Agency (JST), Kawaguchi, Saitama, Japan.
authors: Miwa
authors: M
authors: Haruta
authors: Department of Biomedical Research Center, Division of Analytical Science, Faculty of Medicine, Saitama Medical University, Moroyama, Saitama, Japan.
authors: Narumi
authors: N
authors: Hirosawa
authors: Department of Obstetrics and Gynecology, Faculty of Medicine, Saitama Medical University, Moroyama, Saitama, Japan.
authors: Motoharu
authors: M
authors: Suzuki
authors: Division of Immunology, Aichi Cancer Center Research Institute, Nagoya, Japan.
authors: Minako
authors: M
authors: Tatsumi
authors: Division of Immunology, Aichi Cancer Center Research Institute, Nagoya, Japan.
authors: Norihiro
authors: N
authors: Ueda
authors: Division of Immunology, Aichi Cancer Center Research Institute, Nagoya, Japan.
authors: Hiroyuki
authors: H
authors: Maki
authors: Department of Stem Cell Biology and Regenerative Medicine, Graduate School of Medical Science, Kansai Medical University, Hirakata, Osaka, Japan.
authors: Ryusuke
authors: R
authors: Nakatsuka
authors: Department of Stem Cell Biology and Regenerative Medicine, Graduate School of Medical Science, Kansai Medical University, Hirakata, Osaka, Japan.
authors: Yoshikazu
authors: Y
authors: Matsuoka
authors: Department of Stem Cell Biology and Regenerative Medicine, Graduate School of Medical Science, Kansai Medical University, Hirakata, Osaka, Japan.
authors: Yutaka
authors: Y
authors: Sasaki
authors: Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan.
authors: Shinobu
authors: S
authors: Tsuzuki
authors: Division of Oncological Pathology, Aichi Cancer Center Research Institute, Nagoya, Japan.
authors: Hayao
authors: H
authors: Nakanishi
authors: Transcriptome Research Group, National Institute of Radiological Sciences, Chiba, Japan.
authors: Ryoko
authors: R
authors: Araki
authors: Transcriptome Research Group, National Institute of Radiological Sciences, Chiba, Japan.
authors: Masumi
authors: M
authors: Abe
authors: Department of Hematology and Oncology, Fujita Health University, Toyoake, Aichi, Japan.
authors: Yoshiki
authors: Y
authors: Akatsuka
authors: Department of Biomedical Research Center, Division of Analytical Science, Faculty of Medicine, Saitama Medical University, Moroyama, Saitama, Japan.
authors: Yasushi
authors: Y
authors: Sakamoto
authors: Department of Stem Cell Biology and Regenerative Medicine, Graduate School of Medical Science, Kansai Medical University, Hirakata, Osaka, Japan.
authors: Yoshiaki
authors: Y
authors: Sonoda
authors: Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors: Yasuharu
authors: Y
authors: Nishimura
authors: Division of Immunology, Aichi Cancer Center Research Institute, Nagoya, Japan.
authors: Kiyotaka
authors: K
authors: Kuzushima
authors: Division of Immunology, Aichi Cancer Center Research Institute, Nagoya, Japan. CREST, Japan Science and Technology Agency (JST), Kawaguchi, Saitama, Japan. yuemura@east.ncc.go.jp senjusat@gpo.kumamoto-u.ac.jp.
authors: Yasushi
authors: Y
authors: Uemura
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000276:immunology; D000954:Antigens, Surface / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D005260:Female; D016130:Immunophenotyping; D008545:Melanoma / Q000276:immunology / Q000473:pathology / Q000628:therapy; D051379:Mice; D022423:Myeloid Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D009369:Neoplasms / Q000276:immunology; D010455:Peptides / Q000276:immunology; D010641:Phenotype; D039904:Pluripotent Stem Cells / Q000166:cytology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D016207:Cytokines; D010455:Peptides