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Generation of the humanized-liver mouse from human iPS cell-derived cholangiocytes

Research Project

Project/Area Number 24700439
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Laboratory animal science
Research InstitutionCentral Institute for Experimental Animals

Principal Investigator

HIGUCHI Yichiro  公益財団法人実験動物中央研究所, その他部局等, 研究員 (00596281)

Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2012: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywordsヒト化肝臓マウス / ヒトiPS細胞 / 胆管上皮細胞 / HepaRG細胞 / 肝臓 / ヒト肝蔵マウス
Research Abstract

Humanized-liver mice, in which the liver has been repopulated with human hepatocytes, have been used to study aspects of human liver physiology such as drug metabolism, toxicology and hepatitis infection. However, the procurement of human hepatocytes is a major problem in producing humanized-liver mice because of the finite nature of the patient-derived resource.
In this study, I focused on the cholangiocytes as donor cell source for liver reconstitution since former studies demonstrated the differentiation potential of cholangiocytes (Furuyama et al, Nat. Genet, 2011, Shimper-Ronan et al., Development, 2006). To evaluate the liver reconstitution potential, cholangiocytes that purified from mouse liver, or induced from human iPS cells, were transplanted into the injured liver mouse model. As a result, both of cholangiocytes did not show the liver reconstitution. These results indicate that normal cholangiocytes are not suitable for the donor cell source of humanized-liver mice.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • Research Products

    (4 results)

All 2014

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 1 results) Presentation (2 results)

  • [Journal Article] A Novel Enhanced Green FluorescentProtein-Expressing NOG Mouse for Analyzingthe Microenvironment of Xenograft Tissues2014

    • Author(s)
      Yuichiro Higuchi, Kenji Kawai, Masafumi Yamamoto, Miyuki Kuronuma, Yasuhiko Ando, Ikumi Katano, Masato Nakamura, Hiroshi Suemizu
    • Journal Title

      Experimental Animals

      Volume: 63 Issue: 1 Pages: 55-62

    • DOI

      10.1538/expanim.63.55

    • NAID

      130003391611

    • ISSN
      0007-5124, 1341-1357, 1881-7122
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The human hepatic cell line HepaRG cells, possible cell source for steady generation of humanized liver TK-NOG mice2014

    • Author(s)
      Higuchi, Y., Kawai, K., Yamazaki, H., Nakamura, M., Bree, F., Guillouzo, C., and Suemizu, H.
    • Journal Title

      Xenobiotica

      Volume: 27 Issue: 2 Pages: 146-157

    • DOI

      10.3109/00498254.2013.836257

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Presentation] HepaRG細胞を用いたヒト化肝臓マウスの作成2014

    • Author(s)
      樋口裕一郎、川井健司、山崎洋志、中村雅登、Franxoise Bree, Christiane Guguen-Guillouzo、末水洋志
    • Organizer
      第13回日本再生医療学会総会
    • Place of Presentation
      国立京都国際会館
    • Related Report
      2013 Final Research Report
  • [Presentation] HepaRG細胞を用いたヒト化肝臓マウスの作成2014

    • Author(s)
      樋口裕一郎、川井健司、山崎洋志、中村雅登、Francoise Bree、Christiane Guguen-Guilllouzo、末水洋志
    • Organizer
      第13回日本再生医療学会総会
    • Place of Presentation
      国立京都国際会館
    • Related Report
      2013 Annual Research Report

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Published: 2013-05-31   Modified: 2019-07-29  

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