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Rapid and enhanced repolarization in sandwich-cultured hepatocytes on an oxygen-permeable membrane

Paper ID Volume ID Publish Year Pages File Format Full-Text
3898 197 2010 8 PDF Available
Title
Rapid and enhanced repolarization in sandwich-cultured hepatocytes on an oxygen-permeable membrane
Abstract

In this study, we established rat primary hepatocyte sandwich cultures on oxygen-permeable membranes and investigated the change in their repolarization. Functional bile canaliculi in sandwich-cultured hepatocytes on oxygen-permeable polydimethylsiloxane (PDMS) membranes were re-established more quickly than those in a conventional sandwich culture on polystyrene (PS). This enhanced biliary excretory activity was also observed in hepatocytes on another oxygen-permeable membrane plate but not on a PDMS surface whose oxygen permeability is blocked. An apical efflux transporter protein, Mrp2, was more rapidly distributed in hepatocytes cultured on PDMS membranes than in hepatocytes cultured on conventional PS plates. Moreover, the area of distribution of the Mrp2 in polarized hepatocytes cultured on PDMS membranes was more widespread than that for the hepatocytes grown on sandwich-cultured PS plates. The observation of ultrastructure in transmission electron microscopy clearly confirmed the presence of bile canalicular lumens possessing microvilli and tight junctions. Additionally, we demonstrated that the 7-ethoxyresorufin-O-deethylation activity of hepatocytes on PDMS membranes was also improved as compared to those on a PS surface. Therefore, sandwich-cultured hepatocytes on oxygen-permeable substrates can provide a simple tool for predicting the hepatic metabolism and toxicity of xenobiotics in vivo with short span and low cost in the course of drug discovery and evaluation.

Keywords
Drug development; Hepatocyte; Oxygen-permeable membrane; Sandwich culture; Polarity; Biliary excretion
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Rapid and enhanced repolarization in sandwich-cultured hepatocytes on an oxygen-permeable membrane
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biochemical Engineering Journal - Volume 52, Issues 2–3, 15 November 2010, Pages 255–262
Authors
, , , , , , ,
Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us