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Ng SS, Xiong A, Nguyen K, et al. Long-term culture of human liver tissue with advanced hepatic functions. JCI Insight. 2017;2(11)doi: 10.1172/jci.insight.90853.
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. (2017). Long-term culture of human liver tissue with advanced hepatic functions. JCI insight, 2(11), . https://doi.org/10.1172/jci.insight.90853
Ng, Soon Seng, et al. "Long-term culture of human liver tissue with advanced hepatic functions." JCI insight vol. 2,11 (2017). doi: https://doi.org/10.1172/jci.insight.90853
Ng SS, Xiong A, Nguyen K, Masek M, No DY, Elazar M, Shteyer E, Winters MA, Voedisch A, Shaw K, Rashid ST, Frank CW, Cho NJ, Glenn JS. Long-term culture of human liver tissue with advanced hepatic functions. JCI Insight. 2017 Jun 02;2(11). doi: 10.1172/jci.insight.90853. eCollection 2017 Jun 02. PMID: 28570275; PMCID: PMC5453699.
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JCI Insight. 2017 Jun 02;2(11). doi: 10.1172/jci.insight.90853. eCollection 2017 Jun 02.

Long-term culture of human liver tissue with advanced hepatic functions.

JCI insight

Soon Seng Ng, Anming Xiong, Khanh Nguyen, Marilyn Masek, Da Yoon No, Menashe Elazar, Eyal Shteyer, Mark A Winters, Amy Voedisch, Kate Shaw, Sheikh Tamir Rashid, Curtis W Frank, Nam Joon Cho, Jeffrey S Glenn

Affiliations

  1. Division of Gastroenterology and Hepatology, Department of Medicine.
  2. Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, USA.
  3. School of Materials Science and Engineering, Nanyang Technological University, Singapore, Singapore.
  4. Department of Pathology, Stanford University School of Medicine.
  5. Department of Bioengineering, Stanford University, Stanford California, USA.
  6. Department of Pediatric Gastroenterology and Nutrition, Shaare Zedek Medical Center, Jerusalem, Israel.
  7. Department of Obstetrics and Gynecology.
  8. Department of Chemical Engineering, Stanford University, Stanford California, USA.

PMID: 28570275 PMCID: PMC5453699 DOI: 10.1172/jci.insight.90853

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.

Keywords: Drug screens; Gastroenterology; Hepatitis; Infectious disease; Pharmacology

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