1993 Fiscal Year Final Research Report Summary
Development of hybrid artificial liver system
| Project/Area Number |
03404038
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Digestive surgery
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| Research Institution | Hokkaido University |
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Principal Investigator |
UCHINO Junichi Hokkaido University School of Medicine, Professor, 医学部, 教授 (40000989)
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| 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)
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| Project Period (FY) |
1991 – 1993
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| Keywords | Hybrid artificial liver system / Culture of hepatocyte / Hepatic failure / Natural antibody / Human hepatocyte / Warm ischemia / Hepatic function |
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| 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
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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
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[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
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[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)
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「研究成果報告書概要(欧文)」より
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[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
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[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
