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

• 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
• ISSN: 0173-0835; 1522-2683; 1522-2683
• DOI: 10.1002/elps.201000122

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.