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EXPERIMENTAL STUDY ON DEVELOPMENT OF BIOARTIFICIAL LIVER

Research Project

Project/Area Number 05670464
Research Category

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

Allocation TypeSingle-year Grants
Research Field Gastroenterology
Research InstitutionGIFU UNIVERSITY

Principal Investigator

OHNISHI Hiroo  GIFU UNIVERSITY SCHOOL OF MEDICINE,ASSISTANT PROFESSOR, 医学部附属病院, 講師 (40176954)

Co-Investigator(Kenkyū-buntansha) SUGIHARA Junichi  GIFU UNIVERSITY SCHOOL OF MEDICINE,ASSISTANT PROFESSOR, 医学部附属病院, 講師 (70216323)
Project Period (FY) 1993 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1995: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1994: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1993: ¥700,000 (Direct Cost: ¥700,000)
KeywordsExtracellular matrix / EHS gel / Primary cultured hepatocyte / Liver-specific functions / Albumin production / Ammonia detoxication / Hollow fiber cartridge / EHSgel / ブタ急性虚血性肝不全 / 動脈血ケント体比 / 肝癌由来株化細胞 / 肝細胞特異機能 / PVLA / 転写因子 / 転写制御因子
Research Abstract

Culturing hepatocytes on different extracellular matrix (ECM) substrata including tissue culture plastic, type I collagen, Engelbreth-Holm-Swarm (EHS) gel and poly-N-p-vinylbenzyl-D-lactonamide (PVLA) regulated levels of mRNAs for cytoskeleton and liver specific genes. In hepatocytes on EHS gel, the ratio of albumin/beta-actin in mRNA levels was high and serially increased during cultute period, while the ratio was low and declined in cells on plastic substratum, type I collagen or PVLA.The changes in cellular levels of albumin mRNA which were regulated by ECM corresponded with those in the liver-specific transcription factor, hepatocyte nuclear factor-4 (HNF-4), which controls the the transcription of liver-specific genes.
A most important feature in the design of bioartificial liver is that bioreactor cells retain highly differentiated functions for prolonged periods. Hepatocyte functions were evaluated in perfused bioreactors, each containing of primary rat hepatocytes or transformed human liver cells (Hep G2) entrapped in EHS gel in hollow fiber modules. In vitro application of a gel entrapment bioartificial liver showed that albumin secretion and ureogenesis were observed to a greater extent in rat hepatocytes than in Hep G2 cells. The hybrid liver support system was developed consisting of plasma perfusion through porous hollow fiber modules inoculated with porcine hepatocytes in EHS gel. The system was examined in pigs with ischemic liver failure. During bioartificial liver support treatment, pigs with liver failures decreased serum ammonia levels. These findings suggested that primary hepatocyte was superior to the Hep G2 cell line as the source of hepatic function in a bio-artificial liver and that EHS gel hepatocyte culture system which combined with a hollow fiber module had useful advantages for bioartificial liver.

Report

(4 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • 1993 Annual Research Report
  • Research Products

    (13 results)

All Other

All Publications (13 results)

  • [Publications] 永木正仁: "ハイブリッド型人工肝" 医学と薬学. 31. 305-312 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 永木正仁: "ハイブリッド型バイオ人工肝研究の動向" 日本臨床. 52. 2205-2213 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Masahito Nagaki: "Regulation of hepatic genes and liver transcription factors in rat hepatocytes by extracellular matrix" Biochem Biophys Res Commun. 210. 38-43 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 内藤智雄: "ハイブリッド型バイオ人工肝開発の基礎的検討 初代培養ラット肝細胞の培養系におよぼす劇症肝炎患者血漿の影響" 岐阜大学医学部紀要. 43. 282-291 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Masahito Nagaki, et al: "Development of a hybrid bioartificial liver." Jpn J Clin Med. 52. 2205-2213 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Masahito Nagaki, et al: "Regulation of hepatic genes and liver transcription factors in rat hepatocytes by extracellular matrix." Biochem Biophys Res Commun. 210. 38-43 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Tomoo Naito: "Experimental studies on the development of a hybrid bioartificial liver. Effects of plasma of patients with fulminant hepatic failure on the liver functions of cultured rat hepatocytes." Act Shol Med Univ Gifu. 43. 282-291 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Masahito Nagaki: "Regulation of hepatic genes and liver transcription factors in rat hepatocytes by extracellular matrix" Biochemical and Biophysical Research Communications. 210. 38-43 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 永木 正仁: "細胞外マトリックスと肝細胞増殖、分化機能制御作用" 肝細胞骨格研究会誌. 5. 61-65 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 永木 正仁: "ハイブリッド型バイオ人工肝研究の動向" 日本臨床. 52. 2205-2213 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 永木 正仁: "ハイブリッド型人工肝" 医学と薬学. 31. 305-312 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 内藤 智雄: "ハイブリッド型バイオ人工肝開発の基礎的検討 初代培養ラット肝細胞の培養系" 岐阜大学紀要. (印刷中).

    • Related Report
      1994 Annual Research Report
  • [Publications] 永木正仁: "ハイブリッド型人工肝" 医学と薬学. 31. 305-312 (1994)

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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