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 10(7) 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 amino acid profile in the serum. These findings indicate that this system may be a useful model for an artificial liver support. (c) 1996 John Wiley & Sons, Inc.

journal_name

Biotechnol Bioeng

authors

Shiraha H,Koide N,Hada H,Ujike K,Nakamura M,Shinji T,Gotoh S,Tsuji T

doi

10.1002/(SICI)1097-0290(19960520)50:4<416::AID-BIT

subject

Has Abstract

pub_date

1996-05-20 00:00:00

pages

416-21

issue

4

eissn

0006-3592

issn

1097-0290

journal_volume

50

pub_type

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