Engineered Liver Platforms for Different Phases of Drug Development

Drug-induced liver injury (DILI) remains a leading cause of drug withdrawal from human clinical trials or the marketplace. Owing to species-specific differences in liver pathways, predicting human-relevant DILI using in vitro human liver models is crucial. Microfabrication tools allow precise contro...

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Bibliographic Details
Published in:Trends in biotechnology (Regular ed.) 2017-02, Vol.35 (2), p.172-183
Main Authors: Ware, Brenton R, Khetani, Salman R
Format: Article
Language:English
Subjects:
Adenoviruses
Animals
Clinical trials
Drug Evaluation, Preclinical - instrumentation
Drug Evaluation, Preclinical - methods
drug-induced liver injury
Enzymes
Equipment Design
Humans
Internal Medicine
Liver - drug effects
Liver - physiology
Liver diseases
Liver, Artificial
liver-on-a-chip
Metabolism
Metabolites
microfabrication
micropatterned co-cultures
Organ Culture Techniques - instrumentation
Organ Culture Techniques - methods
Pharmaceutical industry
primary human hepatocytes
Proteins
Rodents
Spheroids
Tissue Engineering - instrumentation
Tissue Engineering - methods
Tissue Scaffolds
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Summary:Drug-induced liver injury (DILI) remains a leading cause of drug withdrawal from human clinical trials or the marketplace. Owing to species-specific differences in liver pathways, predicting human-relevant DILI using in vitro human liver models is crucial. Microfabrication tools allow precise control over the cellular microenvironment towards stabilizing liver functions for weeks. These tools are used to engineer human liver models with different complexities and throughput using cell lines, primary cells, and stem cell-derived hepatocytes. Including multiple human liver cell types can mimic cell–cell interactions in specific types of DILI. Finally, organ-on-a-chip models demonstrate how drug metabolism in the liver affects multi-organ toxicities. In this review we survey engineered human liver platforms within the needs of different phases of drug development.
ISSN:0167-7799
1879-3096
DOI:10.1016/j.tibtech.2016.08.001