Institute of Lung Health and Immunity (LHI) and Comprehensive Pneumology Center (CPC); Member of the German Center for Lung Research (DZL), Helmholtz Munich, Munich, Germany.
Institute of Lung Health and Immunity (LHI) and Comprehensive Pneumology Center (CPC); Member of the German Center for Lung Research (DZL), Helmholtz Munich, Munich, Germany.
Eur J Pharm Sci. 2022 Dec 1;179:106305. doi: 10.1016/j.ejps.2022.106305. Epub 2022 Oct 8.
The development of biomimetic in vitro lung models as an alternative to animal studies is urgent to improve the predictability of the pharmacokinetics of potential new drugs. For pharmacokinetics studies, advanced in vitro lung models such as lung-chips should mimic a functional air-blood barrier. Unlike in vivo conditions, stem/primary cells and cell lines do not necessarily form a functional and tight barrier when cultured in vitro. Here, we explore the two gold standard techniques for monitoring barrier integrity: transepithelial electrical resistance (TEER) and permeability. We discuss the advantages and limitations of these methods, provide recommendations for methodological improvements, and we elude on possible future directions.
仿生体外肺模型的发展作为替代动物研究的方法迫在眉睫,以提高潜在新药药代动力学的预测能力。对于药代动力学研究,先进的体外肺模型如肺芯片应模拟功能性的气-血屏障。与体内条件不同,干细胞/原代细胞和细胞系在体外培养时不一定形成功能性和紧密的屏障。在这里,我们探索了两种监测屏障完整性的金标准技术:跨上皮电阻(TEER)和通透性。我们讨论了这些方法的优缺点,提出了改进方法的建议,并探讨了可能的未来方向。