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Development of bioartificial liver support utilizing hepatocyte spheroids and its evaluation on pigs with liver failure.

Research Project

Project/Area Number 07457595
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionOkayama University

Principal Investigator

KOIDE Norio  Okayama University, Medical School Hospital, lecturer, 医学部・附属病院, 講師 (20142333)

Co-Investigator(Kenkyū-buntansha) HAMAZAKI Keisuke  Okayama University, Medical School Hospital, lecturer, 医学部・附属病院, 講師 (90172965)
TANAKA Noriaki  Okayama University, Medical School, professor, 医学部, 教授 (10127566)
Project Period (FY) 1995 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1997: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1996: ¥800,000 (Direct Cost: ¥800,000)
KeywordsSpheroid / Artificail liver support / Circulating culture / Liver failure / Serum ammonia level / Pig / 肝細胞スフェロイド / アルブミン産生 / アンモニア処理能 / 急性肝不全 / 尿素合成 / 劇症肝炎 / 連続培養
Research Abstract

A bio-artificial liver support utilizing hepatocyte multicellular spheroids (spheroid) were developed. Isolated rat or porcine hepatocytes were allowd to form spheroids in the primary culture using chemically defined medium and culture substrates of proteoglycans and their analogs. For the large scale production of spheroid porcine hepatocytes were cultured in the multilayr-plates pre-coated with neo-proteoglycan that was chemically synthesized with chondroitin sulfate and phosphatidyl ethanolamine. Functional level of the spheroids were evaluated with the activities of p-450s, albumin production and urea production. A bio-artificial liver support system was consisted with a closed circuit to which a bioreactor chambercontaining hapatocyte spheroids was inserted. The closed circuit was equipped with a regulator unit that automatically regulated the levels of dissolved oxygen and pH in the circulating medium. A hollow fiber cartridge for plasma exchange or a spouted bed chamber were used as the bioreactor chamber. The performance of the bio-artificial liver support system was evaluated on pigs with acute liver failure experimentally induced by the administration of D-galactosamine. The reductio of serum ammonia level was observed in all of the pigs treated with bio-artificial liver support system. However no significant improvement of the survival rate was seen, though the elongation of survival time was in some pigs. These result obtained with hepatocyte spheroid equivalent to about 10% of liver cell volume in vivo.

Report

(4 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • 1995 Annual Research Report
  • Research Products

    (34 results)

All Other

All Publications (34 results)

  • [Publications] Shinji T, Koide N, et al.: "Reciprocal gene expression of rat fibroglycan and β-actin during the course of regeneration after D-galactosamine liver injury." Hepato-Gastroenterology. 44・4. 239-244 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 小出 典男、辻 孝夫: "肝細胞スフェロイドをバイオリアクターとするハイブリッド型人工肝臓の開発" 「肝臓」. 38・4. 280-284 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 小出 典男: "人工肝に必要な機能" 組織培養工学. 23・8. 284-287 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Oka T, Koide N, et al.: "Transient appearance of perisinusoidal chondroitin sulfate proteoglycans associated with enhanced expression of biglycan gene during D-galactosamine-induced acute liver injury in rats." Hepatology Research. 8・6. 164-175 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Song X-J, Muramatsu H, et al.: "The serum level of midkine, a heparin-binding growth factor, as a tumor marker." Biomedical Research. 8・5. 375-381 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Endo C, Kusachi S, et al.: "Time-dependent increase in sydecan-I and fibroglycan messenger RNA expression in the infarct zone after experimentally induced myocardial infarction in rats." Coronary Artery Disease. 8・2. 155-161 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 小出 典男、辻 孝夫: "肝臓病学の最前線1997" 肝細胞スフェロイドをバイオリアクターとするハイブリッド型人工肝臓の開発, 409 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Shinji T,Koide N,et al.: "Reciprocal gene expression of rat fibroglycan and beta -actin during the course of regeneration after D-galactosamine liver injury." Hepato-Gastroenterology. 44. 239-244 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Koide N,Tsuji T: "A hybrid type bio-artificial liver support system utilizing hepatocyte spheroids as a bioreactor." Kanzo. 38 (4). 280-284 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Oka T,Koide N,et al.: "Transient appearance of perisinusoidal condrotin sulfate proteoglycans associated with enhanced expression of biglycan gene during D-galactosamine-induced acute liver injury in rats." Hepatology Research. 8. 164-175 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Song X-J,Muramatsu H,et al.: "The serum level of midkine, a heparin-biding growth factor, as a tumor marker." Biomedical Research. 18 (5). 375-381 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Endo C,Kusachi S,et al.: "Time-dependent increase in sydecan-1 and fibroglycan messenger RNA expression in the infarct zone after experimentally induced myocardial infarction in rats." COronary Artery Disease. 8. 155-161 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Koide N.Tsuji T: A bio-artificial liver support system utilizing hepatocyte spheroids as a bioreactor. Frontier of Hepatology 1997. eds by Yamanaka M,et al Tyugaiigkusya, tokyo, 351-356 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Shinji T,Koide N,et al: "Reciprocal gene expression of rat fibroglycan and β-actin during the course of regeneration after D-galactosamine liver injury." Hepato-Gastroenterology. 44・4. 239-244 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 小出典男、辻孝夫: "肝細胞スフェロイドをバイオリアクターとするハイブリッド型人工肝臓の開発" 「肝臓」. 38・4. 280-284 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 小出典男: "人工肝に必要な機能" 組織培養工学. 23・8. 284-287 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Oka T,Koide N,et al.: "Transient appearance of perisinusoidal chondroitin sulfate proteoglycans associated with enhanced expression of biglycan gene during D-galactosamine-induced acute liver injury in rats." Hepatology Research. 8・6. 164-175 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Song X-J,Muramatsu H,et al: "The serum level of midkine,a heparin-biding growth factor,as a tumor marker." Biomedical Research. 8・5. 375-381 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Endo C,Kusachi S,et al: "Time-dependent increase in sydecan-1 and fibroglycan messenger RNA expression in the infarct zone after experimentally induced myocardial infarction in rats." Coronary Artery Disease. 8・2. 155-161 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 小出典男、辻孝夫: "肝臓病学の最前線1997" 肝細胞スフェロイドをバイオリアクターとするハイブリッド型人工肝臓の開発, 409 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Sasaki S,Koide N,et al.: "Immunohistochemica study of proteoglycans in O-galactosamine-induced acute hepatitis in rats." J Gastroenterol. 31(1). 46-54 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yada T,Koide N,et al.: "Transferent accumulation of perisimusoidal chondroitin sulfate proteoglycans during liver development and regeneration." J Histochem Cytochem. 44(9). 969-980 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Morita T,Hada H,et al.: "Detection of hepattitis C virus RNA in circulating immune complexes by RT-PCR." Hepaato-Gatroenterol. 43(3). 582-585 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Muramatsu H,Xiao-jun S,et al.: "Enzyme-linked Immunoassay of Midkine and Its Application in Evaluation of Midkine Levels in the Developing Mouse Brain and in Sera from Pateints with Hepatocellular Carcinoma." J Biochem. 119(6). 1171-1175 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Niwa T,Sakatani T,et al.: "Cytochrome p450s of isolated rat hepatocytes in spheroid and monolayer cultures." Res Commun Molecular Pathology and Pharmacology. 91(3). 372-377 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Shiraha H,Koide N,et al.: "Improve ment of serum amino acid profile in hepatic failure with the bio-artificial liver using multicellular hepatocyte spheroids." Biotechnology & Bioengineering. 50(4). 416-421 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 小出典男、白羽英則、他: "人工臓器への応用、細胞外マトリックス-臨床医学への応用- 編集渡辺明治、岡崎 薫" メデイカルレビュー社, 519 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Tamura T,Koide N,et al.: "Gene expression of the liver-specific proteins,albumin and trasferin,in well conserved in hepatocyte spheroid" Acta Med Okayama,. 49(3). 161-167 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Hirasaki S,Koide N,et al.: "A family with herediatary serum cholinesterase deficiency." Internal Medicine. 34. 632-635 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Sasaki S,Koide N,et al.: "Immunohistochemica study of proteoglycans in d-galactosamine-induced acute hepatitis in rats." J Gastroenterol. 31. 46-54 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Yumoto Y,Hanafusa T,et al.: "Loss of heterozygosity and analysis of mutation of p53 in hepatocellular carcinoma." J Gastroenterl Hepatol. 10. 179-185 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Shiraha H,Koide N,et al.: "Improvement of serum amino acid profile in hepatic failure with the bio-artificial liver using multicellular hepatocyte spheroids." Biotechnology & Bioengineering. (in perss). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] 白羽英則、小出典男、他: "ラット肝細胞spheroidをbioreactorとするhollow fiber型人工肝臓の開発." 人工臓器. 24. 740-743 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 小出典男: "肝の生化学.箱根シンポジューム6" 肝再生におけるマトリックスremodeling-特にコンドロイチン硫酸プロテオグリカンを中心として., 235 (1995)

    • Related Report
      1995 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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