1997 Fiscal Year Final Research Report Summary
Development of bioartificial liver support utilizing hepatocyte spheroids and its evaluation on pigs with liver failure.
| Project/Area Number |
07457595
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Okayama University |
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Principal Investigator |
KOIDE Norio Okayama University, Medical School Hospital, lecturer, 医学部・附属病院, 講師 (20142333)
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| 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)
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| Project Period (FY) |
1995 – 1997
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| Keywords | Spheroid / Artificail liver support / Circulating culture / Liver failure / Serum ammonia level / Pig |
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| 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.
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