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|Title:||Long-term culture of human liver tissue with advanced hepatic functions||Authors:||Xiong, Anming
Ng, Soon Seng
No, Da Yoon
Winters, Mark A.
Rashid, Sheikh Tamir
Frank, Curtis W.
Cho, Nam Joon
Glenn, Jeffrey S.
|Issue Date:||2017||Source:||Ng, S. S., Xiong, A., Nguyen, K., Masek, M., No, D. Y., Elazar, M., Shteyer, E., et al. (2017). Long-term culture of human liver tissue with advanced hepatic functions. JCI Insight, 2(11), e90853-. doi:10.1172/jci.insight.90853||Series/Report no.:||JCI Insight||Abstract:||A major challenge for studying authentic liver cell function and cell replacement therapies is that primary human hepatocytes rapidly lose their advanced function in conventional, 2-dimensional culture platforms. Here, we describe the fabrication of 3-dimensional hexagonally arrayed lobular human liver tissues inspired by the liver’s natural architecture. The engineered liver tissues exhibit key features of advanced differentiation, such as human-specific cytochrome P450–mediated drug metabolism and the ability to support efficient infection with patient-derived inoculums of hepatitis C virus. The tissues permit the assessment of antiviral agents and maintain their advanced functions for over 5 months in culture. This extended functionality enabled the prediction of a fatal human-specific hepatotoxicity caused by fialuridine (FIAU), which had escaped detection by preclinical models and short-term clinical studies. The results obtained with the engineered human liver tissue in this study provide proof-of-concept determination of human-specific drug metabolism, demonstrate the ability to support infection with human hepatitis virus derived from an infected patient and subsequent antiviral drug testing against said infection, and facilitate detection of human-specific drug hepatotoxicity associated with late-onset liver failure. Looking forward, the scalability and biocompatibility of the scaffold are also ideal for future cell replacement therapeutic strategies.||URI:||https://hdl.handle.net/10356/90007
|DOI:||10.1172/jci.insight.90853||Rights:||© 2017 American Society for Clinical Investigation (ASCI). This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/bync/4.0/), permitting all non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.||Fulltext Permission:||open||Fulltext Availability:||With Fulltext|
|Appears in Collections:||MSE Journal Articles|
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