Basic Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 14, 2017; 23(2): 204-215
Published online Jan 14, 2017. doi: 10.3748/wjg.v23.i2.204
Three-dimensional perfused human in vitro model of non-alcoholic fatty liver disease
Tomasz Kostrzewski, Terri Cornforth, Sophie A Snow, Larissa Ouro-Gnao, Cliff Rowe, Emma M Large, David J Hughes
Tomasz Kostrzewski, Terri Cornforth, Sophie A Snow, Larissa Ouro-Gnao, Cliff Rowe, Emma M Large, David J Hughes, CN Bio Innovations Limited, Welwyn Garden City AL7 3AX, United Kingdom
Author contributions: Kostrzewski T performed the majority of experiments and analysed the data; Cornforth T, Snow SA, Ouro-Gnao L performed experimental analysis; Kostrzewski T, Cornforth T, Rowe C, Large EM and Hughes DJ designed and coordinated the research; Kostrzewski T and Hughes DJ wrote the paper; all authors read and reviewed the paper.
Supported by Innovate UK (Technology Strategy Board) Advancing the Development and Application of Non-Animal Technologies Project: 3D cell culture model for studying Non-Alcoholic Fatty Liver Disease (NAFLD) - Ref: 131720.
Conflict-of-interest statement: At the time of this study all authors were employees of CN Bio Innovations Ltd.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: David Hughes, DPhil, CN Bio Innovations Limited, BioPark, Broadwater Rd, Welwyn Garden City AL7 3AX, United Kingdom.
Telephone: +44-1707-358739
Received: August 16, 2016
Peer-review started: August 17, 2016
First decision: October 11, 2016
Revised: October 25, 2016
Accepted: November 16, 2016
Article in press: November 16, 2016
Published online: January 14, 2017
Core Tip

Core tip: We report the development of an in vitro, fully human, three-dimensional cell culture model of non-alcoholic fatty liver disease (NAFLD). The model recapitulates key features of clinical NAFLD, with primary human hepatocytes continuously loaded with fat, for up to 14 d of culture, without causing any hepatotoxicity. Fat loading caused transcriptomic, proteomic and metabolic changes to the hepatocytes, including reduced activity of CYP3A4 and CYP2C9 enzymes. Fat loading in the model could be modulated using known anti-steatotic drugs (e.g., metformin), demonstrating the utility of the model for screening the efficacy of novel anti-steatotic compounds.