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Liver sinusoid on a chip: Long‐term layered co‐culture of primary rat hepatocytes and endothelial cells in microfluidic platforms
Author(s) -
Kang Young Bok Abraham,
Sodunke Temitope R.,
Lamontagne Jason,
Cirillo Joseph,
Rajiv Caroline,
Bouchard Michael J.,
Noh Moses
Publication year - 2015
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/bit.25659
Subject(s) - sinusoid , hepatocyte , biology , in vivo , liver disease , microbiology and biotechnology , cell culture , liver cell , liver cancer , viral replication , cell , virus , virology , cancer research , in vitro , immunology , medicine , biochemistry , hepatocellular carcinoma , genetics
We describe the generation of microfluidic platforms for the co‐culture of primary hepatocytes and endothelial cells; these platforms mimic the architecture of a liver sinusoid. This paper describes a progressional study of creating such a liver sinusoid on a chip system. Primary rat hepatocytes (PRHs) were co‐cultured with primary or established endothelial cells in layers in single and dual microchannel configurations with or without continuous perfusion. Cell viability and maintenance of hepatocyte functions were monitored and compared for diverse experimental conditions. When primary rat hepatocytes were co‐cultured with immortalized bovine aortic endothelial cells (BAECs) in a dual microchannel with continuous perfusion, hepatocytes maintained their normal morphology and continued to produce urea for at least 30 days. In order to demonstrate the utility of our microfluidic liver sinusoid platform, we also performed an analysis of viral replication for the hepatotropic hepatitis B virus (HBV). HBV replication, as measured by the presence of cell‐secreted HBV DNA, was successfully detected. We believe that our liver model closely mimics the in vivo liver sinusoid and supports long‐term primary liver cell culture. This liver model could be extended to diverse liver biology studies and liver‐related disease research such as drug induced liver toxicology, cancer research, and analysis of pathological effects and replication strategies of various hepatotropic infectious agents. Biotechnol. Bioeng. 2015;112: 2571–2582. © 2015 Wiley Periodicals, Inc.