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Development of a hybrid artificial liver with hepatocytes derived embryonic stem cell for chronic liver failure patients

Research Project

Project/Area Number 16206079
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Biofunction/Bioprocess
Research InstitutionKYUSHU UNIVERSITY

Principal Investigator

KAJIWARA Toshihisa (2005)  Kyushu University, Faculty of Engineering, Professor, 大学院・工学研究院, 教授 (10194747)

船津 和守 (2004)  九州大学, 大学院・工学研究院, 教授 (80037960)

Co-Investigator(Kenkyū-buntansha) MIZUMOTO Hiroshi  Kyushu University, Faculty of Engineering, Associate Professor, 大学院・工学研究院, 助教授 (90346817)
NAKAZAWA Kohji  The University of Kitakyushu, Faculty of Environmental Engineering, Associate Professor, 国際環境工学部, 助教授 (00304733)
梶原 稔尚  九州大学, 大学院・工学研究院, 教授 (10194747)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥49,920,000 (Direct Cost: ¥38,400,000、Indirect Cost: ¥11,520,000)
Fiscal Year 2005: ¥24,960,000 (Direct Cost: ¥19,200,000、Indirect Cost: ¥5,760,000)
Fiscal Year 2004: ¥24,960,000 (Direct Cost: ¥19,200,000、Indirect Cost: ¥5,760,000)
Keywordsembryonic stem cell / organoid / differentiation / hepatocyte / hollow fiber / hybrid artificial liver / regenerative medicine
Research Abstract

We investigated the use of organoid culture technique to mediate hepatocyte differentiation of murine and primate embryonic stem cell. We used our original organoid culture technique, which induce cultured cells to form an organoid in lumen of hollow fibers by centrifugal force.
Mouse ES cells formed an organoid inside of hollow fibers. The ES cell proliferated for more than 20 days of culture and high density culture was achieved. The expressions of mRNAs of hepatocyte specific genes were detected at 15 days of culture, and were sustained for more than 30 days of culture. The functions of albumin secretion and ammonia removal were evaluated under hepatocyte differentiation culture condition. The level of these functions of the ES cells per unit volume of cell culture space increased as culture time, and reached the same level of primary mouse hepatocytes.
Cynomolgus monkey ES cell was also investigated as a model of primate ES cell. Cynomolgus monkey ES cells formed an organoid and expressed some liver-specific functions such as albumin secretion and ammonia removal. The activity of ammonia removal of ES cells organoid per unit volume of cell culture space was roughly comparable to that of primary hepatocytes and human hepatoblastoma cell lines.
In conclusion, our developed novel organoid culture technique directed both mouse and cynomolgus monkey ES cells along a hepatocyte lineage. This culture technique seems to be a promising technique to develop a hybrid artificial liver.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (43 results)

All 2006 2005 2004 Other

All Journal Article (34 results) Book (9 results)

  • [Journal Article] Differentiation effects by the combination of spheroid formation and sodium butyrate treatment in human hepatoblastoma cell line (Hep G2) : a possible cell source for hybrid artificial liver2006

    • Author(s)
      J.Fukuda et al.
    • Journal Title

      Cell Transplantation Vol.14, No.10

      Pages: 819-827

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 肝細胞オルガノイドを利用したハイブリッド型人工肝臓2006

    • Author(s)
      中澤浩二 他
    • Journal Title

      再生医療 Vol.5 Suppl

      Pages: 88-88

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 最新医療を支える成型加工技術の現状2005

    • Author(s)
      中澤浩二 他
    • Journal Title

      プラスチックス 56(9)

      Pages: 147-152

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 人工臓器開発における化学工学の役割2005

    • Author(s)
      水本博 他
    • Journal Title

      ケミカルエンジニヤリング 50(9)

      Pages: 688-693

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] オルガノイド培養法を利用したハイブリッド型人工肝臓の開発2005

    • Author(s)
      青木健太朗 他
    • Journal Title

      化学工学シンポジウムシリーズ 79

      Pages: 80-83

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Differentiation effects by the combination of spheroid formation and sodiumbutyrate treatment in human hepatoblastoma cell line (Hep G2) : a possible cell source for hybrid artificial liver2005

    • Author(s)
      J.Fukuda et al.
    • Journal Title

      Cell Transplantation 14(10)

      Pages: 819-827

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Hepatocyte organoid culture in elliptic hollow fibers to develop a hybrid artificial liver2005

    • Author(s)
      J.Fukuda et al.
    • Journal Title

      The International Journal of Artificial Organs Vol.27, No.12

      Pages: 1091-1099

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The current situation of polymer processing technique to support the latest medical care2005

    • Author(s)
      K.Nakazawa et al.
    • Journal Title

      Japan Plastics Vol.56, No.9

      Pages: 1047-1052

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Role of chemical engineering on artificial organs development2005

    • Author(s)
      H.Mizumoto et al.
    • Journal Title

      Chemical Engineering Vol.50, No.9

      Pages: 688-693

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Development of a hybrid artificial liver using hepatocyte organoid culture2005

    • Author(s)
      K.Aoki et al.
    • Journal Title

      Chemical Engineering Symposium Series 79

      Pages: 80-83

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Differentiation effects by the combination of spheroid formation and sodium butyrate treatment in human hepatoblastoma cell line (Hep G2): a possible cell source for hybrid artificial liver2005

    • Author(s)
      J.Fukuda et al.
    • Journal Title

      Cell Transplantation 14

      Pages: 819-827

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Evaluation of a hybrid artificial liver module with a hepatocyte organoid2005

    • Author(s)
      H.Mizumoto et al.
    • Journal Title

      The International Journal of Artificial Organs 28

      Pages: 197-197

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 人工臓器開発における化学工学の役割2005

    • Author(s)
      水本博 他
    • Journal Title

      ケミカルエンジニヤリング 50

      Pages: 688-693

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 最新医療を支える成形加工技術の現状2005

    • Author(s)
      中澤浩二 他
    • Journal Title

      プラスチックス 56

      Pages: 147-152

    • NAID

      40006893109

    • Related Report
      2005 Annual Research Report
  • [Journal Article] ハイブリッド型人工肝臓の開発におけるこれまでの到達点と今後の課題2005

    • Author(s)
      水本博 他
    • Journal Title

      人工臓器 34

    • NAID

      10016759107

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 肝不全ラットを用いた中空糸/オルガノイド型人工肝臓の性能評価2005

    • Author(s)
      青木健太朗 他
    • Journal Title

      人工臓器 34

    • Related Report
      2005 Annual Research Report
  • [Journal Article] PUF/スフェロイド型人工肝臓モジュール内でのES細胞の肝細胞への分化誘導2005

    • Author(s)
      松本欣也 他
    • Journal Title

      人工臓器 34

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 中空糸/オルガノイド培養法によるES細胞から肝細胞への分化誘導技術の開発2005

    • Author(s)
      野田康一 他
    • Journal Title

      化学工学会第37回秋季大会研究発表講演要旨集

    • Related Report
      2005 Annual Research Report
  • [Journal Article] マウスES細胞のポリウレタン発砲体(PUF)/スフェロイド培養法への適用による肝細胞への分化誘導の試み2005

    • Author(s)
      石原和久 他
    • Journal Title

      再生医療 Vol.4 Suppl

      Pages: 105-105

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 肝細胞オルガノイド培養法を利用したハイブリッド型人工肝臓2004

    • Author(s)
      中澤浩二 他
    • Journal Title

      医工学治療 16(3)

      Pages: 163-167

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Hybrid artificial liver with polyurethane foam / spheroid culture for treatment of acute liver failure2004

    • Author(s)
      T.Kajiwara et al.
    • Journal Title

      Proceedings of The 10th Asian Pacific Confederation of Chemical Engineering Congress

      Pages: 1-7

    • NAID

      130005052456

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Development of a hybrid artificial liver module having liver lobule-like strucuture2004

    • Author(s)
      H.Mizumoto et al.
    • Journal Title

      Proceedings of The 10th Asian Pacific Confederation of Chemical Engineering Congress

      Pages: 1-7

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Organoid-sheet formation for hepatocyte and myocardial cell culture2004

    • Author(s)
      K.Ishihara et al.
    • Journal Title

      Proceedings of The 10th Asian Pacific Confederation of Chemical Engineering Congress

      Pages: 1-9

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] hepatocyte organoid culture in elliptic hollow fibers to develop a hybrid artificial liver2004

    • Author(s)
      J.Fukuda et al.
    • Journal Title

      The International Journal of Artificial Organs 27(12)

      Pages: 1091-1099

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A hybrid artificial liver using hepatocyte organoid2004

    • Author(s)
      K.Nakazawa et al.
    • Journal Title

      Therapeutics & Engineering Vol.16, No.3

      Pages: 163-167

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Hybrid artificial liver with polyurethane foam/spheroid culture for treatment of acute liver failure2004

    • Author(s)
      T.Kajiwara et al.
    • Journal Title

      Proceedings of The 10th Asian Pacific Confederation of Chemical Engineering Congress

      Pages: 1-7

    • NAID

      130005052456

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Development of a hybrid artificial liver module having liver lobule-like structure2004

    • Author(s)
      H.Mizumoto et al.
    • Journal Title

      Proceedings of The 10th Asian Pacific Confederation of Chemical Engineering Congress

      Pages: 1-7

    • NAID

      130005052450

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Establishment of a novel hepatocyte organoid culture and its application to a hybrid artificial liver2004

    • Author(s)
      H.Mizumoto et al.
    • Journal Title

      ABSTRACT BOOK of the Joint Meeting of the Tissue Engineering Society International and the European Tissue Engineering society

      Pages: 264-264

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Evaluation of a hybrid artificial liver module with liver lobule-like structure by applying to a liver failure rat2004

    • Author(s)
      K.Aoki et al.
    • Journal Title

      ABSTRACT BOOK of the Joint Meeting of the Tissue Engineering Society International and the European Tissue Engineering society

      Pages: 263-263

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Development of a hybrid artificial liver module having liver lobule-like strucuture2004

    • Author(s)
      H.Mizumoto et al.
    • Journal Title

      Congress proceedings of the 10th APCChE Cogress (CD-ROM)

      Pages: 1-7

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 急性及び慢性肝不全治療用ハイブリッド型人工肝臓の開発2004

    • Author(s)
      中澤浩二 他
    • Journal Title

      医工学治療 16 Suppl.

      Pages: 61-61

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 肝不全ラットへの適用による中空糸/オルガノイド型人工肝臓の性能評価2004

    • Author(s)
      水本博 他
    • Journal Title

      Organ Biology 11・2

      Pages: 162-162

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Formation of a sheet-shaped organoid using rat hepatocytes for long-term maintenance of liver-specific functions

    • Author(s)
      K.Ishihara et al.
    • Journal Title

      The International Journal of Artificial Organs (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Formation of a sheet-shaped organoid using rat hepatocytes for long-term maintenance of liver-specific functions

    • Author(s)
      K.Ishihara et al.
    • Journal Title

      The International Journal of Artificial Organs (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] 生体工学概論(6.2 人工臓器工学)2006

    • Author(s)
      水本博 他
    • Total Pages
      237
    • Publisher
      コロナ社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] 生体工学概論(6.2節 人工臓器工学)2006

    • Author(s)
      水本博 他
    • Total Pages
      237
    • Publisher
      コロナ社
    • Related Report
      2005 Annual Research Report
  • [Book] 化学工学シンポジウムシリーズ79 診断・治療システムにおける化学工学(第3部3.1)2006

    • Author(s)
      青木健太朗 他
    • Total Pages
      124
    • Publisher
      化学工学会
    • Related Report
      2005 Annual Research Report
  • [Book] Artificial Organs, Bioengineering and Biomedical Engineering, Chap.6, Sec.22005

    • Author(s)
      H.Mizumoto et al.
    • Publisher
      Corona Publishing Co.Ltd.
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] 化学工学ハンドブック(9.4細胞培養工学,9.4.1)2004

    • Author(s)
      水本博 他
    • Total Pages
      591
    • Publisher
      朝倉書店
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] 繊維便覧(第4部門4・11・1節 人工肝臓)2004

    • Author(s)
      福田淳二 他
    • Total Pages
      1009
    • Publisher
      丸善株式会社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] Animal cell culture, Handbook of Chemical Engineering, Chap.9, Sec.9.4.12004

    • Author(s)
      H.Mizumoto et al.
    • Publisher
      Asakura Co.Ltd.
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] Artificial liver, Handbook of Textile, Part.4, Sec.4.11.12004

    • Author(s)
      J.Fukuda et al.
    • Total Pages
      831
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] 化学工学ハンドブック(9.4 細胞培養工学,9.4.1)2004

    • Author(s)
      水本博 他
    • Total Pages
      591
    • Publisher
      朝倉書店
    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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