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Contraction of wild-life iHep cell and development of the evaluation method for metabolism of the top predator

Research Project

Project/Area Number 17K20038
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Research Field Environmental analyses and evaluation and related fields
Research InstitutionHokkaido University

Principal Investigator

Ikenaka Yoshinori  北海道大学, 獣医学研究院, 准教授 (40543509)

Co-Investigator(Kenkyū-buntansha) 川合 佑典  帯広畜産大学, 畜産学部, 助教 (10709546)
鈴木 淳史  九州大学, 生体防御医学研究所, 教授 (30415195)
三谷 曜子  北海道大学, 北方生物圏フィールド科学センター, 准教授 (40538279)
石塚 真由美  北海道大学, 獣医学研究院, 教授 (50332474)
水川 葉月  愛媛大学, 農学研究科, 准教授 (60612661)
中山 翔太  北海道大学, 獣医学研究院, 助教 (90647629)
Project Period (FY) 2017-06-30 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2017: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywords野生動物 / iHep / Metabolism / トッププレデター / P450 / UGT / SULT / 化学物質感受性 / 種差 / 誘導性肝臓様細胞(iHep) / 誘導性肝臓様細胞(iHep)
Outline of Final Research Achievements

The purpose of this study is to develop the evaluation method of metabolism, which is the key to chemical sensitivity, and to clarify the chemical metabolic ability of rare top predator. Fresh liver is required for the evaluation of metabolism, but rare species are difficult to obtain. Therefore, in this study, we attempted to differentiate and induce liver-like cells (iHep cells) from skin fibroblasts by direct reprogramming. First, as a result of this study, we succeeded in culturing fibroblasts of several top predators such as brown bear and Sea lion. Furthermore, as a result of attempting to induce iHep cells using cultured fibroblasts, it was found that the cells were transformed into epithelial cells expressing albumin by introducing a specific factor. In this study, it is highly probable that iHep cells were successfully generated starting from wild animals.

Academic Significance and Societal Importance of the Research Achievements

トッププレデターの化学物質感受性を適切に評価できる実験系は無く、その評価法を確立する必要があった。本研究で一部誘導に成功した野生動物iHep細胞は、野生動物の化学物質感受性を非侵襲的かつ迅速に実施できる。更に、iHep細胞は様々な野生動物獣医療にも応用可能である。例えば、投薬や麻酔による不動化の初期スクリーニングに応用する事で、経験則では無く、科学的根拠に基づいた投与doseの決定が可能となる。これにより、獣医療現場における麻酔中の死亡事故などの減少に通じるだけでなく、将来的には各動物種に応じた創薬への応用も期待できる。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (15 results)

All 2019 2018 2017 Other

All Int'l Joint Research (1 results) Journal Article (7 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 7 results,  Open Access: 3 results) Presentation (7 results) (of which Int'l Joint Research: 4 results)

  • [Int'l Joint Research] カセサート大学(タイ)

    • Related Report
      2017 Research-status Report
  • [Journal Article] Functional and molecular characterization of UDP-glucuronosyltransferase 2 family in cynomolgus macaques2019

    • Author(s)
      Uno Yasuhiro、Takahira Rika、Murayama Norie、Onozeki Shunsuke、Kawamura Shu、Uehara Shotaro、Ikenaka Yoshinori、Ishizuka Mayumi、Ikushiro Shinichi、Yamazaki Hiroshi
    • Journal Title

      Biochemical Pharmacology

      Volume: 163 Pages: 335-344

    • DOI

      10.1016/j.bcp.2019.03.002

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Characterization of function and genetic feature of UDP-glucuronosyltransferase in avian species2019

    • Author(s)
      Kawai Yusuke K.、Shinya So、Ikenaka Yoshinori、Saengtienchai Aksorn、Kondo Takamitsu、Darwish Wageh Sobhy、Nakayama Shota M.M.、Mizukawa Hazuki、Ishizuka Mayumi
    • Journal Title

      Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology

      Volume: 217 Pages: 5-14

    • DOI

      10.1016/j.cbpc.2018.11.001

    • NAID

      120006803956

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Comparison of xenobiotic metabolism in phase I oxidation and phase II conjugation between rats and bird species2018

    • Author(s)
      Saengtienchai A, Ikenaka Y, Kawata M, Kawai Y, Takeda K, Kondo T, Bortey-Sam N, Nakayama S.M.M, Mizukawa H, Ishizuka M.
    • Journal Title

      CBP

      Volume: 214 Pages: 28-35

    • DOI

      10.1016/j.cbpc.2018.08.007

    • NAID

      120006769940

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Molecular and functional characterization of UDP-glucuronosyltransferase 1A in cynomolgus macaques.2018

    • Author(s)
      Uno, Y., Takahira, R., Murayama, N., Ishii, Y., Ikenaka, Y., Ishizuka, M., Yamazaki, H., and Ikushiro, S.
    • Journal Title

      Biochem. Pharmacol.

      Volume: 155 Pages: 172-181

    • DOI

      10.1016/j.bcp.2018.06.027

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The evolution of UDP-glycosyl/glucuronosyltransferase 1E (UGT1E) genes in bird lineages is linked to feeding habits but UGT2 genes is not.2018

    • Author(s)
      Yusuke K. Kawai, Yoshinori Ikenaka, Mayumi Ishizuka, Akira Kubota
    • Journal Title

      PLoS One

      Volume: 13 Issue: 10 Pages: 1-13

    • DOI

      10.1371/journal.pone.0205266

    • NAID

      120006540774

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comparison of xenobiotic metabolism in phase I oxidation and phase II conjugation between rats and bird species2018

    • Author(s)
      Saengtienchai A, Ikenaka Y, Kawata M, Kawai Y, Takeda K, Kondo T, Bortey-Sam N, Nakayama S.M.M, Mizukawa H, Ishizuka M
    • Journal Title

      Comparative Biochemistry & Physiology Part C

      Volume: in press

    • NAID

      120006769940

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Uridine Diphosphate-Glucuronosyltransferase (UGT) 2B Subfamily Interspecies Differences in Carnivores2017

    • Author(s)
      Kondo Takamitsu、Ikenaka Yoshinori、Nakayama Shouta M. M.、Kawai Yusuke K.、Mizukawa Hazuki、Mitani Yoko、Nomiyama Kei、Tanabe Shinsuke、Ishizuka Mayumi
    • Journal Title

      Toxicological Sciences

      Volume: 158 Issue: 1 Pages: 90-100

    • DOI

      10.1093/toxsci/kfx072

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 野生哺乳類における硫酸転移酵素の動物種差解明2018

    • Author(s)
      近藤誉充、池中良徳、中山翔太、水川葉月、三谷曜子、田辺信介 、野見山桂、石塚真由美
    • Organizer
      第27回環境化学討論会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 食肉目動物での第II 相抱合酵素の遺伝的性状および酵素学的性状の解明2018

    • Author(s)
      近藤誉充、池中良徳、中山翔太、水川葉月、三谷曜子、田辺信介 、野見山桂、石塚真由美
    • Organizer
      第45回 日本毒性学会学術年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 鰭脚類を中心とした食肉目の薬物代謝酵素である硫酸転移酵素の種差解明2018

    • Author(s)
      近藤 誉充、池中 良徳、中山 翔太、水川 葉月、三谷 曜子、田辺 信介、野見山 桂、石塚 真由美
    • Organizer
      第24回日本野生動物医学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Inter-species differences of phase II xenobiotics metabolism enzymes in carnivorans.2018

    • Author(s)
      Takamitsu Kondo,Yoshinori Ikenaka, Shouta M.M. Nakayama, Hazuki Mizukawa, Yoko Mitani, Kei Nomiyama, Shinsuke Tanabe, and Mayumi Ishizuka
    • Organizer
      The 6th Sapporo Summer Symposium for One Health (6th SaSSOH)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] UDP-glucuronosyltransferase (UGT) among Pinnipedia and other carnivores2017

    • Author(s)
      Takamitsu Kondo, Yoshinori Ikenaka, Shouta M.M. Nakayama, Yusuke K. Kawai, Hazuki Mizukawa, Yoko Mitani, Kei Nomiyama, Shinsuke Tanabe, and Mayumi Ishizuka
    • Organizer
      the 19th International Symposium on Pollutant Responses in Marine Organisms (PRIMO 19)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] UDP-glucuronosyltransferase (UGT) 2B genetic feature and activities in Carnivores2017

    • Author(s)
      "Takamitsu Kondo, Yoshinori Ikenaka, Shouta M.M. Nakayama, Yusuke K. Kawai, Hazuki Mizukawa, Yoko Mitani, Kei Nomyama, Shinsuke Tanabe, and Mayumi Ishizuka"
    • Organizer
      9th International Toxicology Symposium in Nigeria
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Drug metabolism enzymes in Carnivora species2017

    • Author(s)
      "Takamitsu Kondo, Yoshinori Ikenaka, Shouta M.M. Nakayama, Yusuke K. Kawai, Hazuki Mizukawa, Yoko Mitani, Kei Nomyama, Shinsuke Tanabe, and Mayumi Ishizuka"
    • Organizer
      The 5th Sapporo Summer Seminar for One Health (SaSSOH)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research

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Published: 2017-07-21   Modified: 2020-03-30  

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