Hepatotoxicity assay using human hepatocytes trapped in microholes of a microfluidic device

Hepatocytes have been used for in vitro hepatotoxicity assays because of their ability to sustain intact liver-specific functions. Here, we demonstrate a hepatotoxicity assay system using primary human hepatocytes trapped in microholes of a microfluidic device, providing a microscale in vivo liver-l...

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Bibliographic Details
Published in:Electrophoresis 2010-09, Vol.31 (18), p.3167-3174
Main Authors: Yeon, Ju Hun, Na, Dokyun, Park, Je-Kyun
Format: Article
Language:English
Subjects:
Benzopyrenes - toxicity
Cell Separation - instrumentation
Cell Survival - drug effects
Cell trapping
Chemical and Drug Induced Liver Injury - etiology
Chemical and Drug Induced Liver Injury - pathology
Drug-Related Side Effects and Adverse Reactions
Equipment Design
Hep G2 Cells
Hepatocytes - drug effects
Hepatotoxicity assay
Humans
Microfluidic Analytical Techniques - instrumentation
Microfluidic Analytical Techniques - methods
Microfluidic device
Models, Biological
Primary human hepatocyte
Toxicity Tests - instrumentation
Toxicity Tests - methods
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Summary:Hepatocytes have been used for in vitro hepatotoxicity assays because of their ability to sustain intact liver-specific functions. Here, we demonstrate a hepatotoxicity assay system using primary human hepatocytes trapped in microholes of a microfluidic device, providing a microscale in vivo liver-like environment. We performed microfluidic hepatotoxicity assays of several drugs, including acetaminophen, verapamil, diclofenac, and benzopyrene, all of which are known to specifically affect hepatic function. The drug sensitivities in hepatocytes and HepG2 cells were measured by calculating the live cell fraction at various drug concentrations. The results indicated that hepatocytes were more sensitive to these drugs than HepG2 cells. The lethal concentration 50 values for all drugs tested were similar to those from the in vitro toxicity data with human hepatocytes obtained from the literature. Furthermore, we developed a mathematical hepatotoxicity model based on the time-dependent cell death profiles measured by our device. This novel assay system enabled us to analyze in vivo-like hepatotoxicity in a microfluidic device by exploiting microstructures to mimic the microenvironment of the liver.
ISSN:0173-0835
1522-2683
1522-2683
DOI:10.1002/elps.201000122