Taylor, K., Ram, R., Ewart, L. et al. (9 more authors) (2025) Perspective: How complex in vitro models are addressing the challenges of predicting drug-induced liver injury. Frontiers in Drug Discovery, 5. 1536756. ISSN 2674-0338
Abstract
Predicting which drugs might have the potential to cause drug-induced liver injury (DILI) is highly complex and the current methods, 2D cell-based models and animal tests, are not sensitive enough to prevent some costly failures in clinical trials or to avoid all patient safety concerns for DILI post-market. Animal-based methods are hampered by important species differences in metabolism and adaptive immunity compared to humans and the standard 2D in vitro approaches have limited metabolic functionality and complexity. On 24 April 2023 the Alliance for Human Relevant Science (https://www.humanrelevantscience.org/) hosted a workshop at the Royal Society, London entitled Drug-Induced Liver Injury (DILI): Can Human-Focused Testing Improve Clinical Translation? The conclusion was that complex in vitro models (CIVMs) provide a significant step forward in the safety testing paradigm. This perspective article, written by the participants, builds on those discussions to provide a ‘state of play’ on liver CIVMs with recommendations for how to encourage their greater uptake by the pharmaceutical industry.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2025 Taylor, Ram, Ewart, Goldring, Russomanno, Aithal, Kostrzewski, Bauch, Wilkinson, Modi, Kenna and Bailey. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY - http://creativecommons.org/licenses/by/4.0/). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
Keywords: | DILI; liver injury; in vitro methods; animal testing; replacement; spheroids; microphysiological systems; safety testing |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Engineering (Sheffield) > Department of Chemical and Biological Engineering (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 10 Mar 2025 15:46 |
Last Modified: | 10 Mar 2025 15:46 |
Status: | Published |
Publisher: | Frontiers Media SA |
Refereed: | Yes |
Identification Number: | 10.3389/fddsv.2025.1536756 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:224275 |