用于药物开发不同阶段的工程化肝脏平台
Engineered Liver Platforms for Different Phases of Drug Development.
作者信息
Ware Brenton R, Khetani Salman R
机构信息
School of Biomedical Engineering, Colorado State University, Fort Collins, CO 80523, USA; Department of Bioengineering, University of Illinois at Chicago, Chicago, IL 60607, USA.
Department of Bioengineering, University of Illinois at Chicago, Chicago, IL 60607, USA.
出版信息
Trends Biotechnol. 2017 Feb;35(2):172-183. doi: 10.1016/j.tibtech.2016.08.001. Epub 2016 Sep 2.
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.
药物性肝损伤（DILI）仍然是导致药物从人体临床试验或市场撤出的主要原因。由于肝脏代谢途径存在物种特异性差异，因此使用体外人肝模型预测与人类相关的DILI至关重要。微制造工具能够精确控制细胞微环境，使肝功能稳定数周。这些工具用于利用细胞系、原代细胞和干细胞衍生的肝细胞构建具有不同复杂性和通量的人肝模型。纳入多种人类肝细胞类型可以模拟特定类型DILI中的细胞间相互作用。最后，芯片器官模型展示了肝脏中的药物代谢如何影响多器官毒性。在这篇综述中，我们根据药物开发不同阶段的需求，对工程化人肝平台进行了概述。
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