Double-compartment cell culture apparatus: construction and biochemical evaluation for bioartificial liver support.

Abstract:

:Functional demands on a bioartificial liver support (BAL) device are not limited to biosynthetic activities, but must also encompass metabolic removal of potentially toxic substances. For most BALs, however, the concept and design are exclusively directed to biosynthetic support. To add the ability to metabolize and remove toxic substances, we designed a double-compartment cell culture apparatus (DCCA). Two compartments are separated from each other by a compact epithelial cell sheet spread over a synthetic microporous membrane. When a renal proximal convoluted tubular cell line that had been transduced with the human multidrug-resistant (MDR) gene, PCTL-MDR, was introduced into one of the compartments (hereafter referred to as the "inner" compartment) of the DCCA, a compact cellular monolayer was formed on the membrane. Ammonium ions passed across the membrane, but glucose and its metabolite lactate could not, indicating that the DCCA allowed selective transportation of cellular metabolites. In addition to PCTL-MDR, HepG2, a cell line of hepatic-origin, transduced with CYP3A4 (designated GS-3A4-HepG2), was seeded on the opposite side of the membrane, and the metabolism and transportation of lidocaine were studied. The lidocaine metabolite, monoethylglycinexylidide, was detected in the inner compartment across the PCTL-MDR cell layered membrane, indicating that metabolism and the selective transportation of metabolites between the two compartments occurred by cooperation of renal and hepatic cells. These results suggest that this type of DCCA represents a novel BAL that possesses biotransporting activities, as well as biosynthetic and metabolic activities.

journal_name

Cell Transplant

journal_title

Cell transplantation

authors

Takahashi M,Sakurai M,Enosawa S,Omasa T,Tsuruoka S,Matsumura T

doi

10.3727/000000006783981341

subject

Has Abstract

pub_date

2006-01-01 00:00:00

pages

945-52

issue

10

eissn

0963-6897

issn

1555-3892

journal_volume

15

pub_type

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