Division of Applied Regulatory Science, Office of Translational Science, Office of Clinical Pharmacology, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA.
Office of Clinical Pharmacology, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA.
Clin Pharmacol Ther. 2019 Jul;106(1):139-147. doi: 10.1002/cpt.1458. Epub 2019 Jun 4.
Liver plays a major role in drug metabolism and is one of the main sites of drug adverse effects. Microphysiological systems (MPS), also known as organs-on-a-chip, are a class of microfluidic platforms that recreate properties of tissue microenvironments. Among different properties, the liver microenvironment is three-dimensional, fluid flows around its cells, and different cell types regulate its function. Liver MPS aim to recreate these properties and enable drug testing and measurement of functional endpoints. Tests with these systems have demonstrated their potential for predicting clinical drug effects. Properties of liver MPS that improve the physiology of cell culture are reviewed, specifically focusing on the importance of recreating a physiological microenvironment to evaluate and model drug effects. Advances in modeling hepatic function by leveraging MPS are addressed, noting the need for standardization in the use, quality control, and interpretation of data from these systems.
肝脏在药物代谢中起着重要作用，是药物不良反应的主要发生部位之一。微生理系统（MPS），也称为芯片上器官，是一类微流控平台，可再现组织微环境的特性。在不同的特性中，肝微环境是三维的，细胞周围有流体流动，不同的细胞类型调节其功能。肝 MPS 旨在再现这些特性，并能够进行药物测试和功能终点测量。这些系统的测试已经证明了它们在预测临床药物效果方面的潜力。本文回顾了改善细胞培养生理学的肝 MPS 的特性，特别关注于重建生理微环境以评估和模拟药物作用的重要性。本文还讨论了利用 MPS 来模拟肝功能的进展，并指出需要对这些系统的数据的使用、质量控制和解释进行标准化。
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