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Generation of CYP3A4-expressing human ES/iPS cell-derived hepatocytes for drug screening

Research Project

Project/Area Number 15H06365
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeSingle-year Grants
Research Field Medical pharmacy
Research InstitutionOsaka University

Principal Investigator

Takayama Kazuo  大阪大学, 薬学研究科, 特任助教(常勤) (10759509)

Project Period (FY) 2015-08-28 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
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)
Keywords肝細胞 / ヒトES/iPS細胞 / 薬物代謝 / CYP / 肝毒性 / 創薬試験 / CYP3A4 / ゲノム編集 / 薬物代謝酵素 / 相同組換え
Outline of Final Research Achievements

In this study, we aimed to establish an efficient differentiation method for highly functioning hepatocyte-like cells from human ES/iPS cells. First, we attempted to improve the hepatocyte differentiation method. Next, we developed a method to concentrate the highly functioning hepatocyte-like cells. The hepatic functions of human ES/iPS cell-derived hepatocyte-like cells were enhanced by culturing with conditioned medium of hepatocytes and cholangiocytes. In future, our group is going to establish the genetically engineered human ES/iPS cells, which carry puromycin resistant cassette under the CYP3A4.

Report

(3 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • Research Products

    (19 results)

All 2017 2016 2015

All Journal Article (11 results) (of which Peer Reviewed: 11 results,  Acknowledgement Compliant: 1 results,  Open Access: 6 results) Presentation (6 results) (of which Invited: 2 results) Book (2 results)

  • [Journal Article] Human iPS Cell-Derived Hepatocyte-Like Cells Achieve Zone-Specific Hepatic Properties by Modulation of WNT Signaling2017

    • Author(s)
      Mitani S., Takayama K., Nagamoto Y., Imagawa K., Sakurai F., Tachibana M., Sumazaki R., Mizuguchi H.
    • Journal Title

      Molecular Therapy

      Volume: 25 Pages: 1420-1433

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Isolation and Expansion of Human Pluripotent Stem Cell-derived Hepatic Progenitor Cells by Growth Factor Defined Serum-free Culture Conditions2017

    • Author(s)
      Fukuda T., Takayama K., Hirata M., Liu Y., Yanagihara K., Suga M., Mizuguchi H., Furue M.
    • Journal Title

      Experimental Cell Research

      Volume: 352 Issue: 2 Pages: 333-345

    • DOI

      10.1016/j.yexcr.2017.02.022

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Highly efficient biallelic genome editing of human ES/iPS cells using a CRISPR/Cas9 or TALEN systems2017

    • Author(s)
      Takayama K., Igai K., Hagihara Y., Hashimoto R., Hanawa M., Sakuma T., Tachibana M., Sakurai F., Yamamoto T., Mizuguchi H
    • Journal Title

      Nucleic Acids Research

      Volume: 45 Issue: 9 Pages: 5198-5207

    • DOI

      10.1093/nar/gkx130

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hepatocyte Nuclear Factor 4 Alpha Promotes Definitive Endoderm Differentiation From Human Induced Pluripotent Stem Cells2017

    • Author(s)
      Hanawa M., Takayama K., Sakurai F., Tachibana M., Mizuguchi H.
    • Journal Title

      Stem Cells Reviews & Reports

      Volume: 13 Issue: 4 Pages: 542-551

    • DOI

      10.1007/s12015-016-9709-x

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Generation of a bile salt export pump deficiency model using patient-specific induced pluripotent stem cell-derived hepatocyte-like cells2017

    • Author(s)
      Imagawa K. 1, Takayama K. 1, Isoyama S., Tanikawa K., Shinkai M., Harada K., Tachibana M., Sakurai F., Noguchi E., Hirata K., Kage M., Kawabata K., Sumazaki R., Mizuguchi H.
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 41806-41806

    • DOI

      10.1038/srep41806

    • NAID

      120007135051

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prediction of drug-induced liver injury by using human pluripotent stem cell-derived hepatocyte-like cells.2017

    • Author(s)
      Takayama K., Mizuguchi H.
    • Journal Title

      Drug Metabolism and Pharmacokinetics

      Volume: 32 Issue: 1 Pages: 12-20

    • DOI

      10.1016/j.dmpk.2016.10.408

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prediction of differentiation tendency toward hepatocytes from gene expression in undifferentiated human pluripotent stem cells.2016

    • Author(s)
      Yanagihara K., Liu Y., Kanie K., Takayama K., Okamura M., Hirata M., Fukuda T., Suga M., Nikawa H., Mizuguchi H., Kato R., Furue M.
    • Journal Title

      Stem Cells and Development

      Volume: 25 Pages: 1884-1897

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Laminin 411 and 511 promote the cholangiocyte differentiation of human induced pluripotent stem cells2016

    • Author(s)
      Takayama K., Mitani S., Nagamoto Y., Sakurai F., Tachibana M., Taniguchi Y., Sekiguchi K., Mizuguchi H.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 474 Issue: 1 Pages: 91-96

    • DOI

      10.1016/j.bbrc.2016.04.075

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Modeling of drug-mediated CYP3A4 induction by using human iPS cell-derived enterocyte-like cells2016

    • Author(s)
      Negoro R., Takayama K., Nagamoto Y, Sakurai F., Tachibana M, Mizuguchi H.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 472 Issue: 4 Pages: 631-636

    • DOI

      10.1016/j.bbrc.2016.03.012

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hepatic Maturation of Human iPS Cell-Derived Hepatocyte-Like Cells by ATF5, c/EBPα, and PROX1 Transduction2016

    • Author(s)
      Nakamori D., Takayama K., Nagamoto Y., Mitani S., Sakurai F., Tachibana M., Mizuguchi H.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 469 Issue: 3 Pages: 424-429

    • DOI

      10.1016/j.bbrc.2015.12.007

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Generation of enterocyte-like cells from human induced pluripotent stem cells for drug absorption and metabolism studies in human small intestine2015

    • Author(s)
      Ozawa T., Takayama K., Okamoto R., Negoro R., Sakurai F., Tachibana M., Kawabata K., Mizuguchi H.
    • Journal Title

      Scientific Reports

      Volume: 12 Issue: 1 Pages: 16479-16479

    • DOI

      10.1038/srep16479

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] ヒトES/iPS細胞における高効率相同組換え技術の開発2017

    • Author(s)
      高山和雄、井貝圭佑、櫻井文教、水口裕之
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台
    • Year and Date
      2017-03-25
    • Related Report
      2016 Annual Research Report
  • [Presentation] ヒトES/iPS細胞由来肝臓細胞の作製とその創薬研究への利用2017

    • Author(s)
      高山和雄
    • Organizer
      第6回超異分野学会
    • Place of Presentation
      東京
    • Year and Date
      2017-03-02
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] ヒトES/iPS細胞由来肝細胞の三次元培養による機能向上2016

    • Author(s)
      高山和雄
    • Organizer
      細胞凝集研究会2016
    • Place of Presentation
      札幌
    • Year and Date
      2016-09-09
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] ヒトiPS細胞由来肝細胞の創薬・再生医療への応用2016

    • Author(s)
      高山和雄
    • Organizer
      K-CONNEXスタートアップシンポジウム
    • Place of Presentation
      大阪
    • Year and Date
      2016-01-29
    • Related Report
      2015 Annual Research Report
  • [Presentation] Generation of enterocyte-like cells from human iPS cells for drug absorption and metabolism studies in small intestine2015

    • Author(s)
      Takayama K., Ozawa T., Sakurai F., Tachibana M., Mizuguchi H.
    • Organizer
      日本薬物動態学会第30回年会
    • Place of Presentation
      東京
    • Year and Date
      2015-11-12
    • Related Report
      2015 Annual Research Report
  • [Presentation] ヒト多能性幹細胞から肝細胞様細胞への高効率分化誘導技術の開発―創薬応用を目指して―2015

    • Author(s)
      高山和雄、三村菜摘、萩原康子、立花雅史、櫻井文教、神田勝弘、川端健二、水口裕之
    • Organizer
      第65回日本薬学会近畿支部総会・大会
    • Place of Presentation
      大阪
    • Year and Date
      2015-10-17
    • Related Report
      2015 Annual Research Report
  • [Book] ヒトiPS細胞由来肝細胞の創薬研究・非臨床試験への応用を目指して2015

    • Author(s)
      高山和雄、水口裕之
    • Total Pages
      5
    • Publisher
      薬剤学
    • Related Report
      2015 Annual Research Report
  • [Book] ヒト多能性幹細胞由来肝細胞を用いた次世代型創薬の実現を目指した基盤技術創成2015

    • Author(s)
      高山和雄
    • Total Pages
      6
    • Publisher
      薬学雑誌
    • Related Report
      2015 Annual Research Report

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Published: 2015-08-26   Modified: 2018-03-22  

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