Long-term culture of human liver tissue with advanced hepatic functions
Open accessAbstract
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.
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Basic human liver function was recapitulated by a PEG-based scaffold.
“This result builds on previous work by the authors, in which basic human liver function was recapitulated by a PEG-based scaffold160.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [160]
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- Authors
- Ng, S. S., Xiong, A., Nguyen, K., Masek, M., No, D. Y., Elazar, M., Shteyer, E., Winters, M. A., Voedisch, A., Shaw, K., Rashid, S. T., Frank, C. W., Cho, N. J., & Glenn, J. S.
- Affiliations
- Nanyang Technological University (SG)
- Stanford Medicine (US)
- Shaare Zedek Medical Center (IL)
- Department of Obstetrics and Gynecology,
- Stanford University (US)
- Corresponding author
- Glenn, Jeffrey S.
- ORCID
- Venue
- JCI Insight
- Published
- 2017-06-02
- Volume
- 2
- Issue
- 11
- ISSN
- 2379-3708 (ISSN-L)
- PMC
- PMC5453699
- OpenAlex
- W2620572834
- Cited by
- 32
- References
- 42
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 1 · 2023: 4 · 2022: 5 · 2021: 5 · 2020: 2 · 2019: 5 · 2018: 6
- FWCI
- 3.64
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- JCI Insight (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DR-NTU (Nanyang Technological University) (submittedVersion, cc-by-nc)
- Research Portal (King's College London) (submittedVersion)
- Funders
- Burroughs Wellcome Fund (Clinical Scientist Award in Translational Research (J.S.G.))
- National Research Foundation ((NRF-NRFF2011-01), the National Medical Research Council (NMRC/CBRG/0005/2012))
- National Institutes of Health (U19AI109662 (J.S.G.), RO1AI099245 (J.S.G.))
- Topics
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Keywords
- hepatocyte differentiation, hepatitis C, antiviral drug testing, liver failure, cell replacement therapy, scaffold biocompatibility
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