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Development of hybrid artificial liver system

Research Project

Project/Area Number 03404038
Research Category

Grant-in-Aid for General Scientific Research (A)

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

Principal Investigator

UCHINO Junichi  Hokkaido University School of Medicine, Professor, 医学部, 教授 (40000989)

Co-Investigator(Kenkyū-buntansha) MATUSHITA Michiaki  Hokkaido University School of Medicine, Lecturer, 医学部・附属病院, 講師 (20250425)
NAKAJIMA Yasuaki  Hokkaido University School of Medicine, Lecturer, 医学部・附属病院, 講師 (90198101)
KUZUMAKI Noboru  Hokkaido University School of Medicine, Professor, 医学部, 教授 (80091445)
Project Period (FY) 1991 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥21,800,000 (Direct Cost: ¥21,800,000)
Fiscal Year 1993: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1992: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1991: ¥19,800,000 (Direct Cost: ¥19,800,000)
KeywordsHybrid artificial liver system / Culture of hepatocyte / Hepatic failure / Natural antibody / Human hepatocyte / Warm ischemia / Hepatic function / ヒト肝細胞培養 / 酸素分圧 / バイオリアクター / 培養ブタ肝細胞 / ブタ肝細胞培養 / アミノ酸代謝
Research Abstract

For the clinical application of our hybrid artificial liver system, multiplated hepatocyte monolayrs, the immunological examination on au use of xenogeneic hepatocytes, the methods of isolation and culture of human gepatocytes, and efficacy of the artificial liver system on anhepatic xenogeneic animals were studied.
1. The basic studies on culture of xenogeneic hepatocytes
(1)The functions of cultured porcine hepatocytes had functioned well for 5 days in the plasma from hepatic failure patients. The high levels of the plasma phenylalanine and methonine were reduced significangtly and the molar ratio was improved by the cultured hepatocytes.
(2)Among 103 human sera, seven (6.8%) sera showed cytaotoxicity to cultured porcine hepatocytes. These cytotoxic reactions were thought to be mediated by natural antibodies which belong to an IgM function by an activation of complement system.
2. The studies on isolation and culture of human hepatocytes
(1)The yield of isolated hepatocytes obtained by pe … More rfusing with a mixture of collagenase and dispase was significantly higher than that by perfusing and agitation with a collagenase solution only.
(2)The functions of cultured human hepatocytes were well preserved for 10 days in a Leibovitz L-15 medium or williams'E medium.
(3)Warm ischemia time of the liver tissue affected the yield of isolated hepatocytes. But ather liver tissue tolerated the warm ischemia for up to 120 min. The function of cultured hepatocytes was not affected by warm ischemia till 220 minutes and the hepatocytes exhibited reasonably high levels of hepatic function.
3. The effects of the artificial liver system on anhepatic xenogeneic animals
A small hybrid artificial liver module that contains 5 grams of porcine hepatocytes was manufactured. Ex vivo extracorporeal plasma perfusion studies revealed that the hybrid artificial liver which was heterogeneous to rabbits, showed a tendency to prolong the survival time of anhepatic rabbits. These results indicate that the hybrid artificial liver is a promising artificial liver support system for clinical cases. Less

Report

(4 results)
  • 1993 Annual Research Report   Final Research Report Summary
  • 1992 Annual Research Report
  • 1991 Annual Research Report
  • Research Products

    (34 results)

All Other

All Publications (34 results)

  • [Publications] Uchino J,Matsue H,Takahashi M,Nakajima Y,et al: "A hybrid artificial liver system:function of cultured monoloyer pig hepatocytes in plasma from hepatic failure patients" Trans Am Artif Intern Organs. 37. M337-338 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Nakajima Y,Tsuburaya T,Matsue K,Hamada T,Hase T,Uchino J,et al: "A hybrid artificial liver using primary cultured hepatocytes" Artif Organs Today. 1. 159-170 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 松江弘一、高橋学、濱田朋倫、中島保明、内野純一、熊谷文昭、他: "培養ブタ肝細胞を用いたハイブリッド型人工肝臓の機能評価" 人工臓器. 20. 156-161 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 内野純一、松江弘一、高橋学、濱田朋倫、中島保明、他: "ハイブリッド型人工肝の研究" 外科治療. 65. 470-471 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Takahashi M,Matsue H,Matsushita M,Sato K,Nakajima Y,Uchino J,et al: "Does a porcine hepatocyte hybrid artificial liver prolong the survival time of anhepatic rabbits?" ASAIO J. 38. M468-472 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Takahashi M,Matsue H,Matsushita M,Nakajima Y,Uchino J: "Isolation and culture of human hepatocytes from resected liver tissue as a bioreactor for a hybrid artificial liver" Artif Organs. 17. 653-659 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Takahashi M,Ishikura H,Takahashi C,Nakajima Y,Matsushita M,Uchino J,et al: "Immunologic considerations in the use of cultured porcine hepatocytes as a hybrid artificial liver:anti-porcine hepatocyte human serum" ASAIO J. 39. M242-246 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 内野純一、松下通明、松江弘一、高橋学、西川眞、小池雅彦、田口宏一: "ハイブリッド型人工肝補助装置の現況と課題" 人工臓器. 22. 1145-1149 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Uchino J,Matushita M: "Artificial liver:strategies for the rescue of patients with liver failure" ASAIO J. 40. 74-77 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 松下通明、高橋学、今裕史、蒲池浩文、田口宏一、西川眞、小池雅彦、能登啓光、中島保明、内野純一、他: "ハイブリッド型人工肝への基礎的研究:温阻血時間よりみたヒト肝細胞の単離・培養に関する検討" 人工臓器. 23(印刷中). (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 西川眞、松下通明、松江弘一、高橋学、佐藤和広、能登啓光、田口宏一、小池雅彦、蒲池浩文、今裕史、中島保明、内野純一: "初代培養肝細胞の機能発現に対する至適酸素環境の検討:各酸素分圧下での肝細胞機能" 人工臓器. 23(印刷中). (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Uchino J, Matsue H, Takahashi M, Nakajima Y, Matsushita M, Hamada T, and Hashimura E: "A hybrid artificial liver system : function of cultured monolayr pig hepatocytes in plasma from hepatic failure patients." Trans Am Artif Intern Organs. 37(3). M337-338 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Nakajima Y.Tsuburaya T, Matsue K, Hamada T, Takahashi M, Kumagai F, Hase T, Uchino J, Hashimura E, Komai T, and Kon T: "A hybrid artificial liver using primary cultured hepatocytes." Aritf Organs Today. 1(3). 159-170 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Matsusue H, Takahashi M, Hamada T, Hase T, Nakajima Y, Uchino J, Kumagai F, Tsuburaya T, Hashimura E, Komai T: "The evaluation of an artificial liver system using monolayr culture pig hepatocytes" Jpn J Artif Organs. 20(1). 156-161 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Uchino J, Matsue H, Takahashi M, Hamada T, Nakajima Y, Hashimura E, Komai T: "A hybrid bioartificial liver composed of pig hepatocytes" Surgical Therapy. 65(10). 470-471 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Takahashi M, Matsue H, Matsushita M, Sato K, Nishikawa M, Koike M, Noto H, Nakajima Y, Uchino J, Komai T, and Hashimura E: "Does a porcine hepatocyte hybrid artificial liver prolong the survival time of anhepatic rabbits?" ASAIO J. 38(3). M468-472 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Takahashi M, Matsue H, Matsushita M, Nakajima Y, Uchino J: "Isolation and culture of human hepatocytes from resected liver tissue as a bioreactor for a hybrid artificial liver." Aritf Organs. 17(7). 653-659 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Takahashi M, Ishikura H, Takahashi C, Nakajima Y, Matsushita M, Matsue H, Sato K, Noto H, Taguchi K, Koike M, Nishikawa M, Kamachi H, Kon H, Uchino J, Yoshiki T: "Immunologic considerations in the use of cultured porcine hepatocytes as a hybrid artificial liver : antiporcine hepatocyte human serum." ASAIO J. 39(3). M242-246 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Uchino J, Matsushita M, Matsue H, Takahashi M, Nishikawa M, Koike M, Taguchi K: "Present and future of a hybrid liver support system." Jpn J Artif Organs. 22(4). 1145-1149 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Uchino J and Matsushita M: "Artificial Liver : Strategies for the rescue of patients with liver failure." ASAIO J. 40(1). 74-77 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Matsushita M, Takahashi M, Kon H, Kamachi H, Taguchi K, Nishikawa M, Koike M, Noto H, Sato K, Matsue H, Sato N, Nakajima Y, Une Y, Uchino J: "Baxic study of a hybrid artificial liver : influence of warm ischemia of the surgical liver specimen on hepatocyte isolation and hepatic functions of cultured heuman hepatocytes." Jpn J Artif Organs. 23 (in press). (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Nishikawa M, Matsushita M, Matsue H, Takahashi M, Sato K, Noto H, Taguchi K, Koike M, Kamachi H, Kon H, Nakajima Y, Uchino J: "Effect of oxygen tension on functions of cultured rat hepatocytes." Jpn J Artif Organs. 23 (in press). (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Takahashi M,Matsue H,Matsushita M,Nakajima Y,Uchino J.: "Isolation and culture of human hepatocytes from resected liver tissue as a bioreactor for a hybrid artificial liver" Artificial Organs. 17. 653-659 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Takahashi M,Ishikura H,Nakajima Y,Matsushita M,Uchino J,et al: "Immunologic considerations in the use of cultured porcine hepatocytes as a hybrid artificial liver:anti-porcine hepatocyte human serum" ASAIO Journal. 39. M242-246 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 内野純一,松下通明,松江弘一,高橋学,西川眞,小池雅彦,田口宏一: "ハイブリッド型人工肝補助装置の現況と課題" 人工臓器. 22. 1145-1149 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Uchino J,Matsushita M: "Strategies for the rescue of patients with liver failure" ASIO Journal. 40(印刷中). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] 松下通明、高橋学、今裕史、蒲池浩文、中島保明、内野純一、他: "ハイブリッド型人工肝への基礎的研究:温阻血時間よりみたヒト肝細胞の単離・培養に関する検討" 人工臓器. 23(印刷中). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Manabu Takahashi,Junichi Uchino,et al.: "Does a porcine hepatocyte hybrid artificial liver prolong the survial time of anhepatic rabbits?" ASAIO TRANSACTIONS. 38. 468-472 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 内野 純一,他: "人工臓器1992バイオ型人工肝" 中山書店, 12 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Junichi Uchino et al: "A Hybrid Artificial Liver System Function of Cultured Monolayer Pig Hepatocytes in Plasma from Hepatic Failure Patients" American Society for Artificial Intenal Organs ASAIO. 37. 337-338 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Yasuaki Nakajima et al: "A Hybrid Artificial liver using primary cultured hepatocytes" Artff.Organs Today. 1. 159-170 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 内野 純一他: "ハイブリッド型人工肝の研究" 外科治療. 65. 470-471 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 松江 弘一他: "肝不全ヒト血漿中における培養ブタ肝細胞の機能" 人工臓器. 21. (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] 内野 純一他: "人工臓器1992,“バイオ型人工肝"" 中山書店, (1992)

    • Related Report
      1991 Annual Research Report

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Published: 1991-04-01   Modified: 2016-04-21  

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