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.
School of Biomedical Engineering, Colorado State University, Fort Collins, CO 80523, USA; Department of Bioengineering, University of Illinois at Chicago, Chicago, IL 60607, USA.
Brenton R
BR
Ware
Department of Bioengineering, University of Illinois at Chicago, Chicago, IL 60607, USA. Electronic address: skhetani@uic.edu.
Salman R
SR
Khetani
D000818:Animals; D004353:Drug Evaluation, Preclinical / Q000295:instrumentation* / Q000379:methods; D004867:Equipment Design; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000502:physiology*; D019164:Liver, Artificial; D009924:Organ Culture Techniques / Q000295:instrumentation* / Q000379:methods; D023822:Tissue Engineering / Q000295:instrumentation* / Q000379:methods; D054457:Tissue Scaffolds
drug-induced liver injury; liver-on-a-chip; microfabrication; micropatterned co-cultures; primary human hepatocytes