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Laminar-flow immediate-overlay hepatocyte sandwich perfusion system for drug hepatotoxicity testing

Paper ID Volume ID Publish Year Pages File Format Full-Text
9733 644 2009 10 PDF Available
Title
Laminar-flow immediate-overlay hepatocyte sandwich perfusion system for drug hepatotoxicity testing
Abstract

Drug hepatotoxicity testing requires in vitro hepatocyte culture to maintain the long-term and stable liver specific functions. We developed a drug testing platform based on laminar-flow immediate-overlay hepatocyte sandwich perfusion culture. The immediate-overlay sandwich (collagen-coated porous polymeric membrane as top overlay) protects the cells and integrity of the top collagen matrix from the impact of flow. A bioreactor was designed that allowed proper control of shear stress and mass transfer. The culture parameters such as the optimal perfusion initiation time and flow rate were systematically and mechanistically determined. The optimized system could re-establish hepatocyte polarity to support biliary excretion and to maintain other liver specific functions, such as the biotransformation enzyme activities, for two weeks that extended the usable in vitro hepatocyte-based drug testing window. When the perfusion cultured hepatocytes from days 7 or 14 were used for drug testing, the APAP-induced hepatotoxicity measurements were more sensitive and consistent over time than the static culture control, enabling further exploitations in large-scale drug testing applications.

Keywords
Sandwich culture; Perfusion bioreactor; Mass transfer; Polarity; Shear stress; Stable functions
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Laminar-flow immediate-overlay hepatocyte sandwich perfusion system for drug hepatotoxicity testing
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 30, Issue 30, October 2009, Pages 5927–5936
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