Usefulness and issues of commercially available human iPS cell-derived hepatocytes for toxicity and drug metabolism evaluation (Hepatocyte team, Consortium for safety assessment using human iPS cells, Japan Pharmaceutical Manufacturers Association) – Individual data -

DOI
  • INOUE Tomoaki
    Chugai Pharmaceutical Co., Ltd. Consortium for Safety Assessment using Human iPS Cells Japan Pharmaceutical Manufacturers Association Drug Evaluation Committee Non-Clinical Evaluation Expert Committee
  • IWAZAKI Norihiko
    Mitsubishi Tanabe Pharma Corporation Consortium for Safety Assessment using Human iPS Cells Japan Pharmaceutical Manufacturers Association Drug Evaluation Committee Non-Clinical Evaluation Expert Committee
  • SAITO Fumiyo
    Chemical Evaluation and Research Institute Consortium for Safety Assessment using Human iPS Cells
  • IWAASA Hisashi
    BoZo Research Center Inc. Consortium for Safety Assessment using Human iPS Cells
  • FUTAMURA Mayumi
    BoZo Research Center Inc. Consortium for Safety Assessment using Human iPS Cells
  • TSUTSUMI Yasushi
    Sumika Chemical Analysis Service, Ltd. Consortium for Safety Assessment using Human iPS Cells
  • SATO Ryohei
    Sumika Chemical Analysis Service, Ltd. Consortium for Safety Assessment using Human iPS Cells
  • IZUKAWA Takeshi
    Sumika Chemical Analysis Service, Ltd. Consortium for Safety Assessment using Human iPS Cells
  • ISE Ryota
    Shin Nippon Biomedical Laboratories, Ltd. Consortium for Safety Assessment using Human iPS Cells
  • NAKAMURA Chika
    Shin Nippon Biomedical Laboratories, Ltd. Consortium for Safety Assessment using Human iPS Cells
  • TAMURA Kotaro
    Astellas Pharma Inc. Consortium for Safety Assessment using Human iPS Cells
  • DEAI Yoko
    Astellas Pharma Inc. Consortium for Safety Assessment using Human iPS Cells
  • OHBUCHI Masato
    Astellas Pharma Inc. Consortium for Safety Assessment using Human iPS Cells
  • MORIGUCHI Hiroyuki
    Astellas Pharma Inc. Consortium for Safety Assessment using Human iPS Cells
  • MOTOI Makiko
    Eisai Co., Ltd. Consortium for Safety Assessment using Human iPS Cells
  • WASHIZUKA Masataka
    Zeria Pharmaceutical Co., Ltd. Consortium for Safety Assessment using Human iPS Cells Japan Pharmaceutical Manufacturers Association Drug Evaluation Committee Non-Clinical Evaluation Expert Committee
  • ARAKI Tetsuro
    Asahi Kasei Pharma Corp. Consortium for Safety Assessment using Human iPS Cells Japan Pharmaceutical Manufacturers Association Drug Evaluation Committee Non-Clinical Evaluation Expert Committee
  • TAKABA Katsumi
    Kyowa Hakko Kirin Co., Ltd. Consortium for Safety Assessment using Human iPS Cells
  • AIKAWA Nobuo
    Kyowa Hakko Kirin Co., Ltd. Consortium for Safety Assessment using Human iPS Cells
  • MIKI Atsuko
    LSI Medience Corporation Consortium for Safety Assessment using Human iPS Cells
  • MATSUI Hitoshi
    LSI Medience Corporation Consortium for Safety Assessment using Human iPS Cells
  • TADA Mika
    Taisho Pharmaceutical Co., Ltd. Consortium for Safety Assessment using Human iPS Cells Japan Pharmaceutical Manufacturers Association Drug Evaluation Committee Non-Clinical Evaluation Expert Committee
  • IIDA Izumi
    Taisho Pharmaceutical Co., Ltd. Consortium for Safety Assessment using Human iPS Cells
  • WAKABAYASHI Satoshi
    Taisho Pharmaceutical Co., Ltd. Consortium for Safety Assessment using Human iPS Cells
  • KIYOKAWA Jumpei
    Chugai Pharmaceutical Co., Ltd. Consortium for Safety Assessment using Human iPS Cells
  • NAKAGAWA Toshito
    Chugai Pharmaceutical Co., Ltd. Consortium for Safety Assessment using Human iPS Cells
  • ARUGA Chinami
    Mitsubishi Tanabe Pharma Corporation Consortium for Safety Assessment using Human iPS Cells
  • IWASE Yumiko
    Mitsubishi Tanabe Pharma Corporation Consortium for Safety Assessment using Human iPS Cells
  • MIYOSHI Tomoya
    Toray Industries, Inc. Consortium for Safety Assessment using Human iPS Cells Japan Pharmaceutical Manufacturers Association Drug Evaluation Committee Non-Clinical Evaluation Expert Committee
  • HIGASHI Eriko
    Toray Industries, Inc. Consortium for Safety Assessment using Human iPS Cells
  • MURATA Hiroyuki
    Japan Tabaco Inc. Consortium for Safety Assessment using Human iPS Cells
  • KATAOKA Jiro
    Japan Tabaco Inc. Consortium for Safety Assessment using Human iPS Cells Japan Pharmaceutical Manufacturers Association Drug Evaluation Committee Non-Clinical Evaluation Expert Committee
  • ISHIGURO Naoki
    Nippon Boehringer Ingelheim Co., Ltd. Consortium for Safety Assessment using Human iPS Cells
  • SAITO Asami
    Nippon Boehringer Ingelheim Co., Ltd. Consortium for Safety Assessment using Human iPS Cells
  • HIRUTA Jin
    Nippon Shinyaku Co., Ltd. Consortium for Safety Assessment using Human iPS Cells
  • MORI Nanako
    Nippon Shinyaku Co., Ltd. Consortium for Safety Assessment using Human iPS Cells
  • ISHIZUKA Fumiya
    Nippon Shinyaku Co., Ltd. Consortium for Safety Assessment using Human iPS Cells
  • YAMASHITA Yasuhiro
    Nippon Shinyaku Co., Ltd. Consortium for Safety Assessment using Human iPS Cells
  • KOGA Toshihisa
    Otsuka Pharmaceutical Co., Ltd. Consortium for Safety Assessment using Human iPS Cells
  • YAMAYA Naomitsu
    Otsuka Pharmaceutical Co., Ltd. Consortium for Safety Assessment using Human iPS Cells
  • TOMIDA Takafumi
    Kaken Pharmaceutical Co., Ltd. Consortium for Safety Assessment using Human iPS Cells

Bibliographic Information

Other Title
  • 市販ヒトiPS細胞由来肝細胞の医薬品の毒性・薬物代謝評価系としての有用性，問題点 (日本製薬工業協会　ヒトiPS細胞応用安全性評価コンソーシアム　肝臓チーム) －　個別データ　－

Description

従来から，ヒト初代培養肝細胞は，医薬品開発過程でのin vitroでの薬物代謝・毒性評価に使用されているが，ドナーによる肝機能の差や同じロットの細胞に限りのあることなどから，データのばらつきの原因でもあった。最近，ヒトiPS細胞から分化誘導した肝細胞が市販されるようになり，一定の肝機能を持った細胞が継続して供給され，再現性のあるデータを取得できることが期待されている。本ヒトiPS細胞応用安全性評価コンソーシアム 肝臓チームでは，肝毒性，薬物代謝の評価系に使用する細胞として，ヒトiPS細胞由来肝細胞をヒト初代培養肝細胞と比較し，有用性及び問題点を提示することを目的に，ReproCELLおよびCellectisから市販されているヒトiPS細胞由来肝細胞について評価した。<br>毒性評価では，比較対照細胞としてヒト初代培養肝細胞に加え，肝機能が低いとされているHepG2細胞も用い，ヒトiPS細胞由来肝細胞にCYP阻害剤を加えた系の評価も行なった。既知の肝毒性を示す5化合物について，48時間曝露後のATPおよびLDHを測定し，IC50値や毒性の程度を比較した。<br>代謝評価では，CYP代謝とCYP誘導についてヒト初代培養肝細胞と比較した。CYP代謝活性は，CYP1A1/2，CYP2C9，CYP2C19，CYP2D6，CYP3A4/5について代謝物をLC-MS/MSにて測定した。CYP誘導については，CYP1A2，CYP2B6，CYP3A4について，当該CYPのmRNA発現の測定を行なった。<br>本発表では，実験結果の個別データについて示す。

Journal

Details 詳細情報について

  • CRID
    1390282680525277952
  • NII Article ID
    130005468592
  • DOI
    10.14869/toxpt.41.1.0_p-149
  • Text Lang
    ja
  • Data Source
    • JaLC
    • CiNii Articles
  • Abstract License Flag
    Disallowed

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