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BioMed Research International
Volume 2016, Article ID 1829148, 20 pages
http://dx.doi.org/10.1155/2016/1829148
Review Article

Advances in Engineered Liver Models for Investigating Drug-Induced Liver Injury

1School of Biomedical Engineering, Colorado State University, Fort Collins, CO 80523, USA
2Department of Bioengineering, University of Illinois at Chicago, Chicago, IL 60607, USA

Received 23 April 2016; Accepted 19 July 2016

Academic Editor: Jurgen Borlak

Copyright © 2016 Christine Lin and Salman R. Khetani. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Drug-induced liver injury (DILI) is a major cause of drug attrition. Testing drugs on human liver models is essential to mitigate the risk of clinical DILI since animal studies do not always suffice due to species-specific differences in liver pathways. While primary human hepatocytes (PHHs) can be cultured on extracellular matrix proteins, a rapid decline in functions leads to low sensitivity (<50%) in DILI prediction. Semiconductor-driven engineering tools now allow precise control over the hepatocyte microenvironment to enhance and stabilize phenotypic functions. The latest platforms coculture PHHs with stromal cells to achieve hepatic stability and enable crosstalk between the various liver cell types towards capturing complex cellular mechanisms in DILI. The recent introduction of induced pluripotent stem cell-derived human hepatocyte-like cells can potentially allow a better understanding of interindividual differences in idiosyncratic DILI. Liver models are also being coupled to other tissue models via microfluidic perfusion to study the intertissue crosstalk upon drug exposure as in a live organism. Here, we review the major advances being made in the engineering of liver models and readouts as they pertain to DILI investigations. We anticipate that engineered human liver models will reduce drug attrition, animal usage, and cases of DILI in humans.