Engineered Liver Platforms for Different Phases of Drug Development

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 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Trends in Biotechnology Elsevier

Engineered Liver Platforms for Different Phases of Drug Development

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Publisher
Elsevier Current Trends
Copyright
Copyright © 2016 Elsevier Ltd
ISSN
0167-7799
D.O.I.
10.1016/j.tibtech.2016.08.001
Publisher site
See Article on Publisher Site

Abstract

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.

Journal

Trends in BiotechnologyElsevier

Published: Feb 1, 2017

References

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