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1997 Fiscal Year Final Research Report Summary

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
KeywordsSpheroid / Artificail liver support / Circulating culture / Liver failure / Serum ammonia level / Pig
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.

  • Research Products

    (13 results)

All Other

All Publications (13 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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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

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Published: 1999-03-16  

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