The Significant Improvement of Survival Times and Pathological Parameters by Bioartificial Liver with Recombinant HepG2 in Porcine Liver Failure Model

We developed a bioartificial liver (BAL) containing human hepatoblastoma cell line, HepG2, with the addition of ammonia removal activity by transfecting a glutamine synthetase (GS) gene and estimated the efficacy using pigs with ischemic liver failure. GS-HepG2 cells showed 15% ammonia removal activ...

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Main Authors: Shin Enosawa, Tomoyuki Miyashita, Tomohiro Saito, Takeshi Omasa, Toshiharu Matsumura
Format: Article
Language:English
Published: SAGE Publishing 2006-11-01
Series:Cell Transplantation
Online Access:https://doi.org/10.3727/000000006783981350
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spelling doaj-57487022985b41b6923b074d35cb6dfe2020-11-25T02:48:36ZengSAGE PublishingCell Transplantation0963-68971555-38922006-11-011510.3727/000000006783981350The Significant Improvement of Survival Times and Pathological Parameters by Bioartificial Liver with Recombinant HepG2 in Porcine Liver Failure ModelShin Enosawa0Tomoyuki Miyashita1Tomohiro Saito2Takeshi Omasa3Toshiharu Matsumura4 Department of Innovative Surgery, National Research Institute for Child Health and Development, Tokyo, Japan Department of Innovative Surgery, National Research Institute for Child Health and Development, Tokyo, Japan Epidemiology, National Research Institute for Child Health and Development, Tokyo, Japan Department of Biotechnology, Graduate School of Engineering, Osaka University, Osaka, Japan Roman Industries, Yokohama City, JapanWe developed a bioartificial liver (BAL) containing human hepatoblastoma cell line, HepG2, with the addition of ammonia removal activity by transfecting a glutamine synthetase (GS) gene and estimated the efficacy using pigs with ischemic liver failure. GS-HepG2 cells showed 15% ammonia removal activity of porcine hepatocytes, while unmodified HepG2 had no such activity. The established GS-HepG2 cells were grown in a circulatory flow bioreactor to 3.5–4.1 × 109 cells. Survival time of the animals treated with GS-HepG2 BAL was significantly prolonged compared to the cell-free control (14.52 ± 5.24 h vs. 8.53 ± 2.52 h) and the group treated with the BAL consisting of unmodified wild-type HepG2 (9.58 ± 4.52 h). Comparison showed the cell-containing BAL groups to have significantly fewer incidences of increased brain pressure. Thus, the GS-HepG2 BAL treatment resulted in a significant improvement of survival time and pathological parameters in pigs with ischemic liver failure.https://doi.org/10.3727/000000006783981350
collection DOAJ
language English
format Article
sources DOAJ
author Shin Enosawa
Tomoyuki Miyashita
Tomohiro Saito
Takeshi Omasa
Toshiharu Matsumura
spellingShingle Shin Enosawa
Tomoyuki Miyashita
Tomohiro Saito
Takeshi Omasa
Toshiharu Matsumura
The Significant Improvement of Survival Times and Pathological Parameters by Bioartificial Liver with Recombinant HepG2 in Porcine Liver Failure Model
Cell Transplantation
author_facet Shin Enosawa
Tomoyuki Miyashita
Tomohiro Saito
Takeshi Omasa
Toshiharu Matsumura
author_sort Shin Enosawa
title The Significant Improvement of Survival Times and Pathological Parameters by Bioartificial Liver with Recombinant HepG2 in Porcine Liver Failure Model
title_short The Significant Improvement of Survival Times and Pathological Parameters by Bioartificial Liver with Recombinant HepG2 in Porcine Liver Failure Model
title_full The Significant Improvement of Survival Times and Pathological Parameters by Bioartificial Liver with Recombinant HepG2 in Porcine Liver Failure Model
title_fullStr The Significant Improvement of Survival Times and Pathological Parameters by Bioartificial Liver with Recombinant HepG2 in Porcine Liver Failure Model
title_full_unstemmed The Significant Improvement of Survival Times and Pathological Parameters by Bioartificial Liver with Recombinant HepG2 in Porcine Liver Failure Model
title_sort significant improvement of survival times and pathological parameters by bioartificial liver with recombinant hepg2 in porcine liver failure model
publisher SAGE Publishing
series Cell Transplantation
issn 0963-6897
1555-3892
publishDate 2006-11-01
description We developed a bioartificial liver (BAL) containing human hepatoblastoma cell line, HepG2, with the addition of ammonia removal activity by transfecting a glutamine synthetase (GS) gene and estimated the efficacy using pigs with ischemic liver failure. GS-HepG2 cells showed 15% ammonia removal activity of porcine hepatocytes, while unmodified HepG2 had no such activity. The established GS-HepG2 cells were grown in a circulatory flow bioreactor to 3.5–4.1 × 109 cells. Survival time of the animals treated with GS-HepG2 BAL was significantly prolonged compared to the cell-free control (14.52 ± 5.24 h vs. 8.53 ± 2.52 h) and the group treated with the BAL consisting of unmodified wild-type HepG2 (9.58 ± 4.52 h). Comparison showed the cell-containing BAL groups to have significantly fewer incidences of increased brain pressure. Thus, the GS-HepG2 BAL treatment resulted in a significant improvement of survival time and pathological parameters in pigs with ischemic liver failure.
url https://doi.org/10.3727/000000006783981350
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