Improvement of serum amino acid profile in hepatic failure with the bioartificial liver using multicellular hepatocyte spheroids

Hidenori Shiraha, Norio Koide, Hajime Hada, Kozo Ujike, Masaki Nakamura, Toshiyuki Shinji, Sachiko Gotoh, Takao Tsuji

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

We designed a bioartificial liver support system in which encapsulated multicellular spheroids of rat hepatocytes were utilized as a bioreactor in a hollow fiber cartridge. The spheroids, formed in a positively charged polystyrene dish that contained hormonally defined medium, were encapsulated into microdroplets of agarose that contained about 9 x 107 rat hepatocytes. The medium, including 150 mL reservoir volume, was circulated in a closed circuit in which the cartridge was inserted. The pH and levels of dissolved oxygen were monitored and automatically regulated so that they were maintained within a constant range for 72 h. Albumin accumulated in the circuit at the rate of 2.0 mg/L/h in this system. When the bioreactor cells in the system were replaced with Hep G2 cells, a human hepatoblastoma cell line, albumin accumulated at the rate of 0.15 mg/L/h. The spheroids of primary culture hepatocytes had 13 times higher albumin-producing capacity than the aggregates of Hep G2. The serum of a patient with fulminant hepatic failure was circulated in this system with the spheroids of primary culture hepatocytes. The concentration of branched amino acid (BCAA) in the circuit significantly increased during the 48 h circulation, while the concentration of aromatic amino acid (AAA) and methionine decreased. The ratio of BCAA/AAA increased from 0.640 to 0.772, indicating that the hepatocyte spheroids had improved the imbalance of the amine acid profile in the serum. These findings indicate that this system may be a useful model for an artificial liver support.

Original languageEnglish
Pages (from-to)416-421
Number of pages6
JournalBiotechnology and Bioengineering
Volume50
Issue number4
DOIs
Publication statusPublished - May 20 1996

Fingerprint

Cellular Spheroids
Artificial Liver
Liver Failure
Liver
Amino acids
Hepatocytes
Amino Acids
Albumins
Serum
Aromatic Amino Acids
Bioreactors
Carboxylic acids
Networks (circuits)
Rats
Hepatoblastoma
Acute Liver Failure
Polystyrenes
Hep G2 Cells
Dissolved oxygen
Methionine

Keywords

  • artificial liver
  • encapsulation
  • hollow fiber
  • liver
  • spheroids

ASJC Scopus subject areas

  • Biotechnology
  • Microbiology

Cite this

Improvement of serum amino acid profile in hepatic failure with the bioartificial liver using multicellular hepatocyte spheroids. / Shiraha, Hidenori; Koide, Norio; Hada, Hajime; Ujike, Kozo; Nakamura, Masaki; Shinji, Toshiyuki; Gotoh, Sachiko; Tsuji, Takao.

In: Biotechnology and Bioengineering, Vol. 50, No. 4, 20.05.1996, p. 416-421.

Research output: Contribution to journalArticle

Shiraha, Hidenori ; Koide, Norio ; Hada, Hajime ; Ujike, Kozo ; Nakamura, Masaki ; Shinji, Toshiyuki ; Gotoh, Sachiko ; Tsuji, Takao. / Improvement of serum amino acid profile in hepatic failure with the bioartificial liver using multicellular hepatocyte spheroids. In: Biotechnology and Bioengineering. 1996 ; Vol. 50, No. 4. pp. 416-421.
@article{d022819b8fe541b4840d4a8034250628,
title = "Improvement of serum amino acid profile in hepatic failure with the bioartificial liver using multicellular hepatocyte spheroids",
abstract = "We designed a bioartificial liver support system in which encapsulated multicellular spheroids of rat hepatocytes were utilized as a bioreactor in a hollow fiber cartridge. The spheroids, formed in a positively charged polystyrene dish that contained hormonally defined medium, were encapsulated into microdroplets of agarose that contained about 9 x 107 rat hepatocytes. The medium, including 150 mL reservoir volume, was circulated in a closed circuit in which the cartridge was inserted. The pH and levels of dissolved oxygen were monitored and automatically regulated so that they were maintained within a constant range for 72 h. Albumin accumulated in the circuit at the rate of 2.0 mg/L/h in this system. When the bioreactor cells in the system were replaced with Hep G2 cells, a human hepatoblastoma cell line, albumin accumulated at the rate of 0.15 mg/L/h. The spheroids of primary culture hepatocytes had 13 times higher albumin-producing capacity than the aggregates of Hep G2. The serum of a patient with fulminant hepatic failure was circulated in this system with the spheroids of primary culture hepatocytes. The concentration of branched amino acid (BCAA) in the circuit significantly increased during the 48 h circulation, while the concentration of aromatic amino acid (AAA) and methionine decreased. The ratio of BCAA/AAA increased from 0.640 to 0.772, indicating that the hepatocyte spheroids had improved the imbalance of the amine acid profile in the serum. These findings indicate that this system may be a useful model for an artificial liver support.",
keywords = "artificial liver, encapsulation, hollow fiber, liver, spheroids",
author = "Hidenori Shiraha and Norio Koide and Hajime Hada and Kozo Ujike and Masaki Nakamura and Toshiyuki Shinji and Sachiko Gotoh and Takao Tsuji",
year = "1996",
month = "5",
day = "20",
doi = "10.1002/(SICI)1097-0290(19960520)50:4<416::AID-BIT8>3.0.CO;2-O",
language = "English",
volume = "50",
pages = "416--421",
journal = "Biotechnology and Bioengineering",
issn = "0006-3592",
publisher = "Wiley-VCH Verlag",
number = "4",

}

TY - JOUR

T1 - Improvement of serum amino acid profile in hepatic failure with the bioartificial liver using multicellular hepatocyte spheroids

AU - Shiraha, Hidenori

AU - Koide, Norio

AU - Hada, Hajime

AU - Ujike, Kozo

AU - Nakamura, Masaki

AU - Shinji, Toshiyuki

AU - Gotoh, Sachiko

AU - Tsuji, Takao

PY - 1996/5/20

Y1 - 1996/5/20

N2 - We designed a bioartificial liver support system in which encapsulated multicellular spheroids of rat hepatocytes were utilized as a bioreactor in a hollow fiber cartridge. The spheroids, formed in a positively charged polystyrene dish that contained hormonally defined medium, were encapsulated into microdroplets of agarose that contained about 9 x 107 rat hepatocytes. The medium, including 150 mL reservoir volume, was circulated in a closed circuit in which the cartridge was inserted. The pH and levels of dissolved oxygen were monitored and automatically regulated so that they were maintained within a constant range for 72 h. Albumin accumulated in the circuit at the rate of 2.0 mg/L/h in this system. When the bioreactor cells in the system were replaced with Hep G2 cells, a human hepatoblastoma cell line, albumin accumulated at the rate of 0.15 mg/L/h. The spheroids of primary culture hepatocytes had 13 times higher albumin-producing capacity than the aggregates of Hep G2. The serum of a patient with fulminant hepatic failure was circulated in this system with the spheroids of primary culture hepatocytes. The concentration of branched amino acid (BCAA) in the circuit significantly increased during the 48 h circulation, while the concentration of aromatic amino acid (AAA) and methionine decreased. The ratio of BCAA/AAA increased from 0.640 to 0.772, indicating that the hepatocyte spheroids had improved the imbalance of the amine acid profile in the serum. These findings indicate that this system may be a useful model for an artificial liver support.

AB - We designed a bioartificial liver support system in which encapsulated multicellular spheroids of rat hepatocytes were utilized as a bioreactor in a hollow fiber cartridge. The spheroids, formed in a positively charged polystyrene dish that contained hormonally defined medium, were encapsulated into microdroplets of agarose that contained about 9 x 107 rat hepatocytes. The medium, including 150 mL reservoir volume, was circulated in a closed circuit in which the cartridge was inserted. The pH and levels of dissolved oxygen were monitored and automatically regulated so that they were maintained within a constant range for 72 h. Albumin accumulated in the circuit at the rate of 2.0 mg/L/h in this system. When the bioreactor cells in the system were replaced with Hep G2 cells, a human hepatoblastoma cell line, albumin accumulated at the rate of 0.15 mg/L/h. The spheroids of primary culture hepatocytes had 13 times higher albumin-producing capacity than the aggregates of Hep G2. The serum of a patient with fulminant hepatic failure was circulated in this system with the spheroids of primary culture hepatocytes. The concentration of branched amino acid (BCAA) in the circuit significantly increased during the 48 h circulation, while the concentration of aromatic amino acid (AAA) and methionine decreased. The ratio of BCAA/AAA increased from 0.640 to 0.772, indicating that the hepatocyte spheroids had improved the imbalance of the amine acid profile in the serum. These findings indicate that this system may be a useful model for an artificial liver support.

KW - artificial liver

KW - encapsulation

KW - hollow fiber

KW - liver

KW - spheroids

UR - http://www.scopus.com/inward/record.url?scp=15844431628&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=15844431628&partnerID=8YFLogxK

U2 - 10.1002/(SICI)1097-0290(19960520)50:4<416::AID-BIT8>3.0.CO;2-O

DO - 10.1002/(SICI)1097-0290(19960520)50:4<416::AID-BIT8>3.0.CO;2-O

M3 - Article

VL - 50

SP - 416

EP - 421

JO - Biotechnology and Bioengineering

JF - Biotechnology and Bioengineering

SN - 0006-3592

IS - 4

ER -