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Development of a hybrid artificial liver using artificial blood

Research Project

Project/Area Number 10470249
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionHokkaido University

Principal Investigator

MATSUSHITA Michiaki  Hokkaido Univ., Grad.School of Med., Asso.Pro., 大学院・医学研究科, 助教授 (20250425)

Co-Investigator(Kenkyū-buntansha) OKUBO Hisashi  Hokkaido Univ., Medical Hosp., Physician., 医学部・附属病院, 医員
MURABAYASHI Shun  Hokkaido Univ., Grad.School of Eng., Asso.Pro., 大学院・工学研究科, 助教授 (30200306)
TODO Satoru  Hokkaido Univ., Grad.School of Med., Pro., 大学院・医学研究科, 教授 (60136463)
KAMACHI Hirofumi  Hokkaido Univ., Medical Hosp., Physician, 医学部・附属病院, 医員
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥12,900,000 (Direct Cost: ¥12,900,000)
Fiscal Year 2000: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1999: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1998: ¥8,000,000 (Direct Cost: ¥8,000,000)
KeywordsArtificial liver / Artificial blood / Two channnel hollow fiber / Porcine / mixed liver cell spheroid / Pyridoxalated-Hemoglobin-Polyoxyethylene conjugate : PHP / 肝細胞スフェロイド / 細胞外基質 / コラーゲンゲル / 2系統ホローファイバー / ハイブリッド型人工肝臓 / 酸素消費量
Research Abstract

This project was aimed to make artificial liver using porcine mixed liver cell sphroids, and to evaluate its function.
(1)Mass production of porcine mixed liver cell spheroid
Without chelating agent in cell dispersion, population of non-parenchymal cells were increased, on the contrary, cell viability and yield were decreased. In the collagenase solution, addition of disperse increased the yields and viability of hepatocytes and suppressed the spheroid formation. Production of spheroids could be acheved up to 2.5 x 10^7 cells/ml concentration of hepatocytes in the 1L size spinner flask. Suitable method for porcine liver cell spheroid formation is consisted of rinse with chelating agents, enzyme digestion by collagenase, and spinning culture in 1L sppiner flask with 2.5 x 10^10hepatocytes.
(2)Basic experiments : application of artificial blood for artificial liver
Evaluation of oxygen transport ability of artificial blood was studied in comparison with red blood cells and culture medium in … More vitro. Oxygen supply capability of artificial blood was equal to that of RBC.In addition, oxygen consumption rate of hepatocyte using artificial blood was the highest of all. Artificial blood could be a way to oxygen supply in artificial liver using hepatocytes.
(3)Fabrication and function of artificial liver module
Two channnel hollow fiber module, we have already developed, contained 2g amount of spheroids. The one channnel was for oxygenation and the other was for plasma circulation. Pyricoxalated-Hemoglobin-Polyoxyethylene conjugate : PHP was used as an oxygen carrier in the oxygenation circuit and was compared to the culture medium. Anmonium cloride clearance were higher in the PHP group(32% / 2hr)compared to the control group(7.4% / 2hr), and urea and albumin production were also observed. However, PHP easily leaked from the hollow fiber and transit to the other channnel, so the membrane of the fiber must be changed to fiber with smaller pore size. In addition, as the spheroids enclosed in the extra-capillary space aggregated each other, the function of the module was decreased. Therefore, coating or encapsulation of spheroids are considered to be needed for the maintenance of function. Less

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (37 results)

All Other

All Publications (37 results)

  • [Publications] Kamachi H: "Rat small hepatocytes for liver support : the growth and metabolic activities in culture."Journal of Artificial Organs. 4(in press). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Okubo H.: "Maintenance of morphology and function of mixed liver cell spheroids under collagen gel environment"Journal of Artificial Organs. 4(in press). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 大久保尚: "ミクロ肝臓(混合スフェロイド)の作製と機能-Hybrid型人工肝臓開発に向けて-"組織培養工学. 27(4)(in press). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 大久保尚: "ハイブリッド型人工肝作製をめざした至適大量肝細胞単離法の検討"日本外科学会誌. 100(臨). 558 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Okubo H.: "A New Approach for Rapid Formation of Hepatocyte Spheroids in Rat"Artificial Organs. 23(7). 71 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 蒲池浩文: "増殖能を有する小肝細胞の肝補助への応用に向けた基礎的検討"日本人工臓器学会誌. 29(3). S-111 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 齋藤孝則: "早期形成型ラット肝細胞混合スフェロイド機能維持に向けたコラーゲンゲル環境の検討"北海道外科学会誌. 45(1). 90 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 西川和孝: "多孔性ポリマーフィルムを利用した肝細胞の形態および機能制御"北海道外科学会誌. 45(1). 90 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 大久保尚: "ハイブリッド人工肝臓に向けた肝細胞スフェロイド早期作成法の検討"北海道外科学会誌. 44(1). 80 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 松下通明: "バイオ人工肝臓"組織培養工学. 24(5). 188-192 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 松下通明: "人工臓器-この1年の進歩"人工臓器. 27(5). 804-805 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Noto,H: "Effect of High Concentrations of Bile Acids on Cultured Hepatocytes."Artificial Organs. 22(4). 300-307 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 松下通明: "人工臓器と再生医工学"移植医療,道医シリーズ. 40. 75-78 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hirofumi Kamachi: "Rat small hepatocytes for liver support : the growth and metabolic activities in culture"Journal of Artificial Organs. (in press). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hisashi Okubo: "Maintenance of morphology and function of mixed liver cell spheroids under collagen gel environment"Journal of Artificial Organs. 4(in press). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hisashi Okubo: "Formation of Micro Liver(Mixed liver cell spheroid)and its function-for the development of a hybrid type artificial liver device"The Tissue Culture Engineering. 27(4)(in press). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hisashi Okubo: "Suitable hepatocyte preparation for hibrid-type artificial liver."Journal of Japan Surgical Society. 100. 558 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hisashi Okubo: "A New Approach for Rapid Formation of Hepatocyte Spheroids in Rat"Artificial Organs. 23(7). 71 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hirofumi Kamachi: "The basic study of proliferating small hepatocytes for liver support"Japan Journal of Artificial Organs. 29(3). S-111 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Takanori Saito: "Functional maintenance of mixed liver cell spheroid using collagen gel"The Hokkaido Journal of Surgery. 45(1). 90 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kazutaka Nishikawa: "Control of hepatocytes morphology onto honeycomb patterned films"The Hokkaido Journal of Surgery. 45(1). 90 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hisashi Okubo: "The earlier formation of hepatocyte spheroids for hybroid-type artificial liver."The Hokkaido journal of Surgery. 44(1). 80 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Michiaki Matsushita: "Bioartificial Liver."The Tissue Culture Engineering. 24(5). 188 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Michiaki Matsushita: "Bioartificial liver-Progress in this year."The Japanese Journal of Artificial Organs. 27. 804-805 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hiromitsu Noto: "Effect of High Concentrations of Bile Acids on Cultured Hepatocytes."Artificial Organs. 22(4). 300-307 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Michiaki Matsushita: "Artificial Organ and Tissue Reconstruction."Hokkaido Medical Journal. 40. 75-78 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 蒲池浩文: "増殖能を有する小肝細胞の肝補助への応用に向けた基礎的検討"日本人工臓器学会誌. 29(3). S-111 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 齋藤孝則: "早期形成型ラット肝細胞混合スフェロイド機能維持に向けたコラーゲンゲル環境の検討"北海道外科学会誌. 45(1). 90 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 西川和孝: "多孔性ポリマーフィルムを利用した肝細胞の形態および機能制御"北海道外科学会誌. 45(1). 90 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Okubo H.: "Maintenance of morphology and function of mixed liver cell spheroids under collagen gel environment"Journal of Artificial Organs. 4(in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] 大久保尚: "ミクロ肝臓(混合スフェロイド)の作製と機能〜Hybrid 型人工肝臓開発に向けて〜"組織培養工学. 27(4)(in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] 松下通明: "移植医療,道医シリーズ"人工臓器と再生医工学. 75-78 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 松下 通明: "人工臓器と再生医工学"北海道医報. 938. 6-9 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 松下 通明: "人工肝臓-この1年の進歩" 人工臓器. 27. 804-805 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 松下 通明: "バイオ人工肝臓" 組織培養工学. 24・5. 188 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hiromitsu Noto: "Effect of High Concentrations of Bile Acids on Cultured Hepatocytes" Artificial Organs. 22(4). 300-307 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 大久保 尚: "ハイブリッド型人工肝作製を目指した至適大量肝細胞単離法の検討" 日本外科学会雑誌. 100. 558 (1999)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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