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Long-term maintenance of human hepatocytes in oxygen-permeable membrane bioreactor

Paper ID Volume ID Publish Year Pages File Format Full-Text
11321 731 2006 10 PDF Available
Title
Long-term maintenance of human hepatocytes in oxygen-permeable membrane bioreactor
Abstract

An oxygen-permeable membrane bioreactor utilizing human hepatocytes has been tested in this study. In the bioreactor, human hepatocytes were cultured between flat-sheet gas-permeable polymeric membranes, which ensure the diffusion of O2 and CO2 providing a support for cell anchorage and growth and permit the online observation of the cells with an inverse microscope. This bioreactor allows a direct oxygenation of cells adhered on membranes and of the medium overlaying cells simulating in vivo sinusoidal organization. Human hepatocytes were cultured in the presence of some therapeutic molecules to assess the temporal liver-specific functions of the cells. Interleukin 6 (IL-6), which is a multifactorial proinflammatory cytokine involved in a variety of host defences and pathological processes, and diclofenac, an arylacetic non-steroidal anti-inflammatory drug, were used as therapeutic molecules.The aim of this study was to evaluate the in vitro performance of the small oxygen-permeable membrane bioreactor in the long-term maintenance and differentiation of human hepatocytes under in-vivo-like conditions.The fluid dynamics of the bioreactor were characterized before using it for human cell culture. The functional response to a step challenge in the medium of IL-6 (120 pg/ml), diclofenac (80 μm) and IL-6 and diclofenac together was investigated. The ability of hepatocytes to perform liver-specific functions in terms of urea and albumin synthesis, as well as secretion of total proteins, was maintained for 32 days. Also, the diclofenac biotransformation functions were sustained as the formation of the metabolites 4′-OH-diclofenac and 5-OH-diclofenac lactam demonstrated.This study attested the feasibility of the membrane bioreactor as an in vitro simple model system that allows human hepatocytes to be maintained in a differentiated state similar to that in vivo.

Keywords
Membrane; Human hepatocytes; Bioreactor; Functions; Viability
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Long-term maintenance of human hepatocytes in oxygen-permeable membrane bioreactor
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 27, Issue 27, September 2006, Pages 4794–4803
Authors
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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