Engineered Liver Platforms for Different Phases of Drug Development

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• 作者：Brenton R. Ware¹ ; ² ; Salman R. Khetani² ; ^{skhetani@uic.edu}
• 关键词：liver-on-a-chip ; microfabrication ; micropatterned co-cultures ; drug-induced liver injury ; primary human hepatocytes
• 刊名：Trends in Biotechnology
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：35
• 期：2
• 页码：172-183
• 全文大小：3371 K
• 卷排序：35

文摘

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.