In Vivo Estimation of Bioartificial Liver with Recombinant HepG2 Cells Using Pigs with Ischemic Liver Failure

Biological efficacy of a recombinant human hepatic cell line, glutamine synthetase transfected HepG2 (GS-HepG2), was examined with large-scale culture in a circulatory flow bioreactor and in pigs with ischemic liver failure. GS-HepG2 cells were cultured in a circulatory flow bioreactor from 5 × 107...

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Main Authors: Shin Enosawa, Tomoyuki Miyashita, Yuji Fujita, Seiichi Suzuki, Hiroshi Amemiya, Takeshi Omasa, Shinya Hiramatsu, Kenichi Suga, Toshiharu Matsumura
Format: Article
Language:English
Published: SAGE Publishing 2001-05-01
Series:Cell Transplantation
Online Access:https://doi.org/10.3727/000000001783986459
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author Shin Enosawa
Tomoyuki Miyashita
Yuji Fujita
Seiichi Suzuki
Hiroshi Amemiya
Takeshi Omasa
Shinya Hiramatsu
Kenichi Suga
Toshiharu Matsumura
author_facet Shin Enosawa
Tomoyuki Miyashita
Yuji Fujita
Seiichi Suzuki
Hiroshi Amemiya
Takeshi Omasa
Shinya Hiramatsu
Kenichi Suga
Toshiharu Matsumura
author_sort Shin Enosawa
collection DOAJ
description Biological efficacy of a recombinant human hepatic cell line, glutamine synthetase transfected HepG2 (GS-HepG2), was examined with large-scale culture in a circulatory flow bioreactor and in pigs with ischemic liver failure. GS-HepG2 cells were cultured in a circulatory flow bioreactor from 5 × 107 to 4 × 109 cells for 109 days. The cells showed ammonia removal activity even under substrate (glutamic acid)-free medium, suggesting that the GS catalyzed the activity using intracellular glutamic acid that had been pooled during conventional culture. When GS-HepG2 bioartificial liver (BAL) was applied to pigs with ischemic liver failure, survival time was prolonged to 18.8 ± 6.1 h (mean ± SD, n = 4) from 13.8 ± 5.4 h (n = 6) and 10.7 ± 4.1 h (n = 6) (groups treated with cell-free BAL and treated with plasma exchange and continuous hemodia-filtration, respectively). Laboratory data indicated the tendency for improvement in increase of blood ammonia level and decline of blood coagulation indices in the GS-HepG2 BAL-treated group. The advantages and potential for the cell line as a bioreactor in BAL is also discussed, comparing to those of isolated porcine hepatocytes.
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spelling doaj.art-7a3645f0b5314feca868fedbdfc24c582022-12-21T23:51:54ZengSAGE PublishingCell Transplantation0963-68971555-38922001-05-011010.3727/000000001783986459In Vivo Estimation of Bioartificial Liver with Recombinant HepG2 Cells Using Pigs with Ischemic Liver FailureShin Enosawa0Tomoyuki Miyashita1Yuji Fujita2Seiichi Suzuki3Hiroshi Amemiya4Takeshi Omasa5Shinya Hiramatsu6Kenichi Suga7Toshiharu Matsumura8National Children's Medical Research CenterNational Children's Medical Research CenterNational Children's Medical Research CenterNational Children's Medical Research CenterNational Children's Medical Research CenterUniversity of Osaka, Graduate School of TechnologyUniversity of Osaka, Graduate School of TechnologyUniversity of Osaka, Graduate School of TechnologyMeiji Institute of Health ScienceBiological efficacy of a recombinant human hepatic cell line, glutamine synthetase transfected HepG2 (GS-HepG2), was examined with large-scale culture in a circulatory flow bioreactor and in pigs with ischemic liver failure. GS-HepG2 cells were cultured in a circulatory flow bioreactor from 5 × 107 to 4 × 109 cells for 109 days. The cells showed ammonia removal activity even under substrate (glutamic acid)-free medium, suggesting that the GS catalyzed the activity using intracellular glutamic acid that had been pooled during conventional culture. When GS-HepG2 bioartificial liver (BAL) was applied to pigs with ischemic liver failure, survival time was prolonged to 18.8 ± 6.1 h (mean ± SD, n = 4) from 13.8 ± 5.4 h (n = 6) and 10.7 ± 4.1 h (n = 6) (groups treated with cell-free BAL and treated with plasma exchange and continuous hemodia-filtration, respectively). Laboratory data indicated the tendency for improvement in increase of blood ammonia level and decline of blood coagulation indices in the GS-HepG2 BAL-treated group. The advantages and potential for the cell line as a bioreactor in BAL is also discussed, comparing to those of isolated porcine hepatocytes.https://doi.org/10.3727/000000001783986459
spellingShingle Shin Enosawa
Tomoyuki Miyashita
Yuji Fujita
Seiichi Suzuki
Hiroshi Amemiya
Takeshi Omasa
Shinya Hiramatsu
Kenichi Suga
Toshiharu Matsumura
In Vivo Estimation of Bioartificial Liver with Recombinant HepG2 Cells Using Pigs with Ischemic Liver Failure
Cell Transplantation
title In Vivo Estimation of Bioartificial Liver with Recombinant HepG2 Cells Using Pigs with Ischemic Liver Failure
title_full In Vivo Estimation of Bioartificial Liver with Recombinant HepG2 Cells Using Pigs with Ischemic Liver Failure
title_fullStr In Vivo Estimation of Bioartificial Liver with Recombinant HepG2 Cells Using Pigs with Ischemic Liver Failure
title_full_unstemmed In Vivo Estimation of Bioartificial Liver with Recombinant HepG2 Cells Using Pigs with Ischemic Liver Failure
title_short In Vivo Estimation of Bioartificial Liver with Recombinant HepG2 Cells Using Pigs with Ischemic Liver Failure
title_sort in vivo estimation of bioartificial liver with recombinant hepg2 cells using pigs with ischemic liver failure
url https://doi.org/10.3727/000000001783986459
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