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Studies on the evaluation method for chemical compound toxicity to human hepatocytes by using hollow fiber type three dimensional culture module

Research Project

Project/Area Number 26420804
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Biofunction/Bioprocess
Research InstitutionSojo University

Principal Investigator

MATSUSHITA Taku  崇城大学, 生物生命学部, 教授 (10209538)

Co-Investigator(Kenkyū-buntansha) 石田 誠一  国立医薬品食品衛生研究所, 薬理部, 室長 (10270505)
古水 雄志  崇城大学, 生物生命学部, 助教 (80735829)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords三次元培養 / 胎児肝細胞 / 成人肝細胞 / 化学物質 / 毒性評価 / 亜急性毒性試験 / 動物実験代替法 / 安全性試験
Outline of Final Research Achievements

The toxicity of about 30,000 chemical compounds on the earth should be evaluated by using in vitro cell-based assay system including three-dimensional (3D) culture module. In this research, (1) we have succeeded in the maintenance of the cell viability and CYP3A4 activity of the cryopreserved human hepatocytes for about one mont by perfusion culture using this 3D culture module. (2)We have developed the customized human hepatocyte DNA chip including 188 hepatic function related genes for rapid analysis of hepatic functions of the cells and confirmed the reproducibility of the analysis. (3)It was found by the DNA analysis and so on that the content and activity of mitochondria of fetal hepatocytes were lower than those of adult hepatocytes. And it was suggested that the toxicity differences of several chemical compounds between fetal and adult hepatocytes were depended on their mitochondrial contents and activities.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (43 results)

All 2017 2016 2015 2014 Other

All Journal Article (13 results) (of which Peer Reviewed: 13 results,  Open Access: 6 results,  Acknowledgement Compliant: 4 results) Presentation (27 results) (of which Int'l Joint Research: 2 results,  Invited: 3 results) Remarks (3 results)

  • [Journal Article] Induction of drug resistance in human hepatoma cells cultured on a silicate fiber-based 3D scaffold2017

    • Author(s)
      Mizutami T, Ohta Y, Nakamura M, Komizu Y, Iwasa T, Sasaki K, Watanabe R, Kawabe M, Matsushita T
    • Journal Title

      Advances in Biochemistry and Biotechnology

      Volume: 2017 Pages: 1-5

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Maintenance of viability and functional expression of cryopreserved human hepatocytes using silicate fiber-based 3D scaffold2017

    • Author(s)
      Mizutami T, Ishii T, Komizu Y, Iwasa T, Kawabe M, Togawa N, Matsushita T
    • Journal Title

      Alternatives to Animal Testing and Experimentation

      Volume: 22

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Effects of macroporous hydroxyapatite carriers on the growth and function of human hepatoblasts derived from fetal hepatocytes2016

    • Author(s)
      T. Ishii, H. Saito, Y. Komizu, R. Tomoshige,T. Matsushita
    • Journal Title

      J Biosci Bioeng

      Volume: 22 Issue: 2 Pages: 240-245

    • DOI

      10.1016/j.jbiosc.2016.01.012

    • NAID

      40020927716

    • Related Report
      2016 Annual Research Report 2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Application of 3D culture for human cells as an alternatives to animal experiments2016

    • Author(s)
      Matsushita T
    • Journal Title

      Alternatives to Animal Testing and Experimentation.

      Volume: 21 Pages: 50-51

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A culture method of rat hepatocytes using the three-dimensional cell cultre scaffold “Cellbed” and its application for liver toxicity testing2016

    • Author(s)
      Iwasa T, Watanabe R, Sasaki K, Matsushita T, Yamaguchi A, Kawabe M
    • Journal Title

      Alternatives to Animal Testing and Experimentation

      Volume: 21 Pages: 52-56

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Upregulations of metallothionein gene expressions and tolerance to heavy metal toxicity by three dimensional cultivation of HepG2 cells on VECELL 3-D inserts2016

    • Author(s)
      T. Kubo, Y. Kuroda, S. Horiuchi, SR. Kim, Y. Sekino, S. Ishida
    • Journal Title

      The Journal of Toxicological Sciences

      Volume: 41 Issue: 1 Pages: 147-153

    • DOI

      10.2131/jts.41.147

    • NAID

      130005119790

    • ISSN
      0388-1350, 1880-3989
    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Effects of the use of polyacrylnitrile nanofibers as the 3D scaffolds on the growth and function of human hepatoblasts derived from fetal hepatocytes2015

    • Author(s)
      T. Ishii, Y. Komizu, N. Shibuya, K. Kuasaka, T. Matsushita
    • Journal Title

      Alternatives to Animal Testing and Experimentation

      Volume: 20 Pages: 66-72

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Comparative metabolome analysis of cultured fetal and adult hepatocytes in humans2014

    • Author(s)
      S.-R. Kim, T. Kubo, Y. Kuroda, M. Hojyo, T. Matsuo, A. Miyajima, M. Usami, Y. Sekino, T. Matsushita, S. Ishida
    • Journal Title

      The Journal of Toxicological Sciences

      Volume: 39 Issue: 5 Pages: 717-723

    • DOI

      10.2131/jts.39.717

    • NAID

      130004690958

    • ISSN
      0388-1350, 1880-3989
    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inflammatory cytokines promote the retrodifferentiation of tumor-derived hepatocyte-like cells to progenitor cells2014

    • Author(s)
      H. Dubois-Pot-Schneider, K. Fekir, C. Coulouarn,D. Glaise, C. Aninat, K. Jarnouen, R. Le Guevel, T. Kubo, S. Ishida, F. Morel, A. Corlu
    • Journal Title

      Hepatology

      Volume: 60 Issue: 6 Pages: 2077-2090

    • DOI

      10.1002/hep.27353

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Cell cycle arrest by hybrid liposomes for human lung carcinoma cells2014

    • Author(s)
      Y. Komizu, M. Yukihara, Y. Matsumoto, R. Ueoka
    • Journal Title

      J. Carcinog. Mutagen

      Volume: 5 Issue: 01

    • DOI

      10.4172/2157-2518.1000157

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cepharanthine inhibited HIV-1 cell-cell transmission and cell-free infection via modification of cell membrane fluidity2014

    • Author(s)
      K. Matsuda, S. Hattori, Y. Komizu, R. Kariya, R. Ueoka, S. Okada
    • Journal Title

      Bioorg. Med. Chem. Lett.

      Volume: 24 Issue: 9 Pages: 2115-2117

    • DOI

      10.1016/j.bmcl.2014.03.041

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Immunostimulation Effects of Powder from Barely-<i>Shochu</i> Distillation Remnants on a Human Natural Killer Cell Line <i>in Vitro</i>2014

    • Author(s)
      古水雄志、上岡利子、後藤浩一、上岡龍一
    • Journal Title

      KAGAKU KOGAKU RONBUNSHU

      Volume: 40 Issue: 5 Pages: 438-442

    • DOI

      10.1252/kakoronbunshu.40.438

    • NAID

      130004691070

    • ISSN
      0386-216X, 1349-9203
    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Hybrid nanoparticles inhibit growth of human prostate cancer cells by induction of apoptosis2014

    • Author(s)
      Y. Komizu, T. Ueoka, M. Yukihara, H. Ichihara, Y. Matsumoto, R. Ueoka
    • Journal Title

      SOJ Pharmacy & Pharmaceutical Sciences

      Volume: 1 Pages: 1-4

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 三次元培養担体 Cellbed を用いた肝臓がん細胞の薬剤耐性現象の再現と薬剤耐性克服薬スクリーニングへの応用2017

    • Author(s)
      古水雄志, 中村茉耶, 大田裕也, 水民敬浩, 岩佐卓哉, 佐々木皓平, 渡邊理恵, 川部雅章, 松下琢
    • Organizer
      細胞アッセイ研究会シンポジウム【細胞アッセイ技術の現状と将来】
    • Place of Presentation
      東京大学生産技術研究所コンベンションホール 東京都目黒区
    • Year and Date
      2017-01-31
    • Related Report
      2016 Annual Research Report
  • [Presentation] ヒト細胞三次元培養の代替法としての可能性2016

    • Author(s)
      松下琢
    • Organizer
      第29回日本動物実験代替法学会
    • Place of Presentation
      九州大学百年講堂 福岡県福岡市
    • Year and Date
      2016-11-16
    • Related Report
      2016 Annual Research Report
  • [Presentation] 胎児肝細胞及び成人肝細胞のメタボローム解析と化学物質毒性発現の比較解析(第三報)2016

    • Author(s)
      白木明日香, 市川雄大, 稲村恒亮, 水民敬浩, 古水雄志, 石田誠一, 金秀良, 関野祐子, 松下琢
    • Organizer
      第29回日本動物実験代替法学会
    • Place of Presentation
      九州大学百年講堂 福岡県福岡市
    • Year and Date
      2016-11-16
    • Related Report
      2016 Annual Research Report
  • [Presentation] 三次元培養担体Cellbedを用いた肝がん細胞の薬剤耐性現象の再現と薬剤耐性克服薬スクリーニングへの応用(第二報)2016

    • Author(s)
      中村茉耶, 大田裕也, 水民敬浩, 古水雄志, 岩佐卓哉, 佐々木皓平, 渡邊理恵, 川部雅章, 松下琢
    • Organizer
      第29回日本動物実験代替法学会
    • Place of Presentation
      九州大学百年講堂 福岡県福岡市
    • Year and Date
      2016-11-16
    • Related Report
      2016 Annual Research Report
  • [Presentation] 三次元培養担体Cellbedを用いたヒト凍結肝細胞の機能発現および維持培養における評価2016

    • Author(s)
      長﨑花佳, 稲村恒亮, 水民敬浩, 石井貴晃, 古水雄志, 岩佐卓哉, 佐々木皓平, 渡邊理恵, 川部雅章, 松下琢
    • Organizer
      第29回日本動物実験代替法学会
    • Place of Presentation
      九州大学百年講堂 福岡県福岡市
    • Year and Date
      2016-11-16
    • Related Report
      2016 Annual Research Report
  • [Presentation] Screening of the drugs to overcome drug resistance of human hepatoma HepG2 cells by using three-dimentional culture2016

    • Author(s)
      Mizutami T, Ohta Y, Komizu Y, Matsushita T
    • Organizer
      17th International Biotechnology Symposium and Exhibition (IBS2016)
    • Place of Presentation
      Melbourne Convention Centre, Melbourne, Australia
    • Year and Date
      2016-10-24
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ヒト肝がん細胞三次元培養の薬剤耐性克服薬スクリーニングへの応用2016

    • Author(s)
      穴田春奈, 中村茉耶, 大田裕也, 水民敬浩, 古水雄志, 松下琢
    • Organizer
      第53回化学関連支部合同九州大会
    • Place of Presentation
      北九州国際会議場 福岡県北九州市
    • Year and Date
      2016-07-02
    • Related Report
      2016 Annual Research Report
  • [Presentation] ハイブリッドリポソームを用いた腫瘍原性肝幹細胞の選択的排除に関する研究2016

    • Author(s)
      稲村恒亮、水民敬浩、古水雄志、松本陽子、上岡龍一、松下 琢
    • Organizer
      第15回日本再生医療学会総会
    • Place of Presentation
      大阪国際会議場(大阪府大阪市)
    • Year and Date
      2016-03-17
    • Related Report
      2015 Research-status Report
  • [Presentation] ハイブリッドリポソームの肝臓がん細胞に対する薬剤耐性克服薬としての応用2016

    • Author(s)
      古水雄志、大田裕也、水民敬浩、松本陽子、上岡龍一、松下 琢
    • Organizer
      国際高等研究所 研究プロジェクト「分子基盤に基づく生体機能への揺らぎとダイナミックネットワークの解明」2015年度第1回研究プロジェクト
    • Place of Presentation
      国際高等研究所(京都府木津川市)
    • Year and Date
      2016-02-18
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] 三次元培養担体 Cellbedを用いた肝がん細胞の薬剤耐性現象の再現と薬剤耐性克服薬スクリーニングへの応用2015

    • Author(s)
      大田裕也、水民敬浩、古水雄志、岩佐卓哉、佐々木皓平、渡邊理恵、川部雅章、松下 琢
    • Organizer
      日本動物実験代替法 学会第28回大会
    • Place of Presentation
      ワークピア横浜(神奈川県横浜市)
    • Year and Date
      2015-12-10
    • Related Report
      2015 Research-status Report
  • [Presentation] 三次元細胞培養担体Cellbedを用いたヒト凍結肝細胞の維持培養2015

    • Author(s)
      石井貴晃、古水雄志、岩佐卓哉、佐々木皓平、渡邊理恵、川部雅章、松下 琢
    • Organizer
      日本動物実験代替法 学会第28回大会
    • Place of Presentation
      ワークピア横浜(神奈川県横浜市)
    • Year and Date
      2015-12-10
    • Related Report
      2015 Research-status Report
  • [Presentation] 胎児肝細胞及び成人肝細胞のメタボローム解析と化学物質毒性発現の比較解析(第二報)2015

    • Author(s)
      市川雄大、松下 琢、石井貴晃、古水雄志、金 秀良、石田誠一、宮島敦子、関野祐子
    • Organizer
      日本動物実験代替法 学会第28回大会
    • Place of Presentation
      ワークピア横浜(神奈川県横浜市)
    • Year and Date
      2015-12-10
    • Related Report
      2015 Research-status Report
  • [Presentation] Screening of the agents to overcome drug resistance of human hepatoma HepG2 cells by using three-dimensional culture2015

    • Author(s)
      T. Mizutami, Y. Ohta, Y. Komizu, T. Matsushita
    • Organizer
      The 4th International Symposium, Dynamic ordering of biomolecular systems for creation of integrated functions
    • Place of Presentation
      Kyushu University Nishijin Plaza(福岡県福岡市)
    • Year and Date
      2015-11-22
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 中空糸膜型三次元細胞培養モジュールを用いたヒト肝細胞の長期培養の実現(2015

    • Author(s)
      松下 琢
    • Organizer
      第45回繊維学会夏季セミナー
    • Place of Presentation
      北九州国際会議場(福岡県北九州市)
    • Year and Date
      2015-07-29
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] ヒト肝臓細胞の中空糸膜型三次元培養モジュールを用いた長期培養と毒性評価への応用2015

    • Author(s)
      石井 貴晃, 古水 雄志, 松下 琢, 柳 麻美子, 生田 健次郎, 日下 孝司
    • Organizer
      第52回化学関連支部合同九州大会
    • Place of Presentation
      北九州国際会議場(福岡県北九州市)
    • Year and Date
      2015-06-27
    • Related Report
      2015 Research-status Report
  • [Presentation] 肝臓機能の維持を目指した中空糸膜型三次元培養モジュールを用いたヒト肝細胞の長期培養2015

    • Author(s)
      石井貴晃、松下琢、古水雄志、柳麻美子、生田健次郎、日下孝司
    • Organizer
      第14回日本再生医療学会総会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2015-03-19 – 2015-03-21
    • Related Report
      2014 Research-status Report
  • [Presentation] ヒト肝臓がん細胞の三次元培養による薬剤耐性克服薬のスクリーニングへの応用2014

    • Author(s)
      水民敬浩、大田裕也、石井貴晃、古水雄志、松下 琢
    • Organizer
      日本動物実験代替法学会 第29回大会
    • Place of Presentation
      横浜国立大学(神奈川県横浜市)
    • Year and Date
      2014-12-05 – 2014-12-07
    • Related Report
      2014 Research-status Report
  • [Presentation] 毒性評価への応用を目指した中空糸膜型三次元細胞培養モジュールを用いたヒト肝細胞の長期培養2014

    • Author(s)
      石井貴晃、松下琢、古水雄志、柳麻美子、生田健次郎、日下孝司
    • Organizer
      日本動物実験代替法学会 第29回大会
    • Place of Presentation
      横浜国立大学(神奈川県横浜市)
    • Year and Date
      2014-12-05 – 2014-12-07
    • Related Report
      2014 Research-status Report
  • [Presentation] 胎児及び成人肝細胞のメタボロームと化学物質毒性発現の比較解析2014

    • Author(s)
      市川雄大、石井貴晃、古水 雄志、松下琢、金秀良、石田誠一、宮島敦子、関野裕子
    • Organizer
      日本動物実験代替法学会 第29回大会
    • Place of Presentation
      横浜国立大学(神奈川県横浜市)
    • Year and Date
      2014-12-05 – 2014-12-07
    • Related Report
      2014 Research-status Report
  • [Presentation] ヒト胎児および成人肝細胞のメタボローム解析による基礎代謝機能と関連する遺伝子発現の比較解析2014

    • Author(s)
      金秀良、久保崇、黒田幸恵、北条麻紀、 宮島敦子、松下琢、関野祐子、石田誠一
    • Organizer
      第58回日本薬学会関東支部大会
    • Place of Presentation
      昭和薬科大学(東京都町田市)
    • Year and Date
      2014-10-04
    • Related Report
      2014 Research-status Report
  • [Presentation] Development of hollow fiber type three dimensional (3D) culture module for long term culture of human hepatocytes to evaluate the drug toxicity to liver2014

    • Author(s)
      T. Matsushita, T. Ishii, N. Shibuya, K. Ikuta, K. Kusaka
    • Organizer
      The 9th World Congress on Alternatives and Animal Use in the Life Sciences
    • Place of Presentation
      チェコ(プラハ)
    • Year and Date
      2014-08-24 – 2014-08-28
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] ヒト胎児肝細胞と成人肝細胞における基礎代謝機能と関連する遺伝子発現の比較解析2014

    • Author(s)
      石田誠一、金秀良、久保崇、 黒田幸恵、北条麻紀、宮島敦子、松下 琢、関野 祐子
    • Organizer
      第41回日本毒性学会学術年会
    • Place of Presentation
      神戸コンベンションセンター(兵庫県神戸市)
    • Year and Date
      2014-07-02 – 2014-07-04
    • Related Report
      2014 Research-status Report
  • [Presentation] 2種類の中空糸膜を用いた三次元細胞培養モジュールの開発2014

    • Author(s)
      石井貴晃、松下琢、渋谷望、生田健次郎、日下孝司
    • Organizer
      日本組織培養学会 第 87 回大会
    • Place of Presentation
      星陵会館(東京都千代田区)
    • Year and Date
      2014-05-29 – 2014-05-30
    • Related Report
      2014 Research-status Report
  • [Presentation] HAp多孔質担体を用いたヒト肝芽細胞の三次元培養とCYP活性の向上2014

    • Author(s)
      伊﨑淳志、石橋孝司、石井貴晃、友重竜一、松下琢
    • Organizer
      日本組織培養学会 第 87 回大会
    • Place of Presentation
      星陵会館(東京都千代田区)
    • Year and Date
      2014-05-29 – 2014-05-30
    • Related Report
      2014 Research-status Report
  • [Presentation] ハイブリッドリポソームを用いた形質転換肝幹細胞の選択的排除2014

    • Author(s)
      稲村恒亮、石井貴晃、押方歩、古水雄志、上岡龍一、松下琢
    • Organizer
      日本組織培養学会 第 87 回大会
    • Place of Presentation
      星陵会館(東京都千代田区)
    • Year and Date
      2014-05-29 – 2014-05-30
    • Related Report
      2014 Research-status Report
  • [Presentation] 肝がん細胞三次元培養の薬剤耐性克服薬スクリーニングへの応用2014

    • Author(s)
      大田裕也、石井貴晃、押方歩、松下 琢
    • Organizer
      日本組織培養学会 第 87 回大会
    • Place of Presentation
      星陵会館(東京都千代田区)
    • Year and Date
      2014-05-29 – 2014-05-30
    • Related Report
      2014 Research-status Report
  • [Presentation] 胎児及び成人肝細胞のメタボロームと化学物質毒性発現の比較解析2014

    • Author(s)
      松下琢, 石井貴晃, 市川雄大, 金秀良, 石田誠一, 宮島敦子, 関野祐子
    • Organizer
      日本組織培養学会 第 87 回大会
    • Place of Presentation
      星陵会館(東京都千代田区)
    • Year and Date
      2014-05-29 – 2014-05-30
    • Related Report
      2014 Research-status Report
  • [Remarks] 崇城大学生物生命学部応用生命科学科医用生体工学講座松下研究室

    • URL

      http://www.life.sojo-u.ac.jp/biomed/matsushita/

    • Related Report
      2016 Annual Research Report
  • [Remarks] 崇城大学研究成果

    • URL

      http://rsrch.ofc.sojo-u.ac.jp/sjuhp/KgApp?kyoinId=ymkbgeyiggy

    • Related Report
      2015 Research-status Report
  • [Remarks] 崇城大学応用生命科学科松下研究室

    • URL

      http://www.life.sojo-u.ac.jp/biomed/matsushita/

    • Related Report
      2015 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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