Application of lung microphysiological systems to COVID-19 modeling and drug discovery: a review.
Application of lung microphysiological systems to COVID-19 modeling and drug discovery: a review.
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DOI：
10.1007/s42242-021-00136-5
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发表时间：
2021
影响因子：
7.9
通讯作者：
Li S
中科院分区：
文献类型：
--
作者：
Sun AM;Hoffman T;Luu BQ;Ashammakhi N;Li S
迫切需要有效的治疗方法来治疗2019年冠状病毒病（COVID-19），这是一种由严重急性呼吸道综合征冠状病毒2（SARS-CoV-2）病毒引起的呼吸道疾病。药物开发的过程是一个成本高昂、节奏严谨的过程，最初有希望的线索的失败往往阻碍了进展。为了应对这一挑战，需要对体外人体微生理系统进行改进和调整，以用于机制研究和药物筛选，从而在大流行危机期间节省宝贵的时间和资源。SARS-CoV-2病毒攻击肺，肺是一个器官，其功能单元的独特三维（3D）结构对于正常的呼吸功能至关重要。体外肺模型基本上概括了不同的组织结构和不同细胞类型之间的动态机械和生物相互作用。目前的模型系统包括Transwell，类器官和器官芯片或微生理系统（MPS）。我们回顾了与COVID-19病理学建模直接相关的模型，包括炎症，水肿，凝血以及肺免疫功能的过程。我们还考虑了可能影响MPS设计和制造的实际问题。在多器官模型的背景下讨论了肺MPS的作用，并讨论了如何将高通量筛选和人工智能与肺MPS相结合，以加速COVID-19和其他传染病的药物开发。
There is a pressing need for effective therapeutics for coronavirus disease 2019 (COVID-19), the respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. The process of drug development is a costly and meticulously paced process, where progress is often hindered by the failure of initially promising leads. To aid this challenge, in vitro human microphysiological systems need to be refined and adapted for mechanistic studies and drug screening, thereby saving valuable time and resources during a pandemic crisis. The SARS-CoV-2 virus attacks the lung, an organ where the unique three-dimensional (3D) structure of its functional units is critical for proper respiratory function. The in vitro lung models essentially recapitulate the distinct tissue structure and the dynamic mechanical and biological interactions between different cell types. Current model systems include Transwell, organoid and organ-on-a-chip or microphysiological systems (MPSs). We review models that have direct relevance toward modeling the pathology of COVID-19, including the processes of inflammation, edema, coagulation, as well as lung immune function. We also consider the practical issues that may influence the design and fabrication of MPS. The role of lung MPS is addressed in the context of multi-organ models, and it is discussed how high-throughput screening and artificial intelligence can be integrated with lung MPS to accelerate drug development for COVID-19 and other infectious diseases.
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影响因子：
41.2
作者：
Chaudhuri O;Gu L;Klumpers D;Darnell M;Bencherif SA;Weaver JC;Huebsch N;Lee HP;Lippens E;Duda GN;Mooney DJ
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影响因子：
3.3
作者：
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通讯作者：
CLEMENTS, JA
DOI：
10.1165/ajrcmb.18.4.2838
发表时间：
1998-04-01
影响因子：
6.4
作者：
Borok, Z;Lubman, RL;Crandall, ED
通讯作者：
Crandall, ED