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An Adverse OutcomesApproach to Study theEffects of SARS-CoV-2 in 3D Organoid Models
Journal of Molecular Biology ( IF 5.6 ) Pub Date : 2021-08-23 , DOI: 10.1016/j.jmb.2021.167213
Amrita Basu 1 , Annapurna Pamreddy 2 , Pragya Singh 2 , Kumar Sharma 3
Affiliation  

The novel SARS-CoV-2 virus outbreak is the major cause of a respiratory disease known as COVID-19. It has caused a global pandemic and has resulted in mortality in millions. The primary mode of infection is respiratory ailments, however, due to multi-organ complications, COVID-19 patients displays a greater mortality numbers. Due to the 3Rs Principle (Refine, Reduce, Replacement), the scientific community has shifted its focus to 3D organoid models rather than testing animal models. 3D organoid models provide a better physiological architecture as it mimics the real tissue microenvironment and is the best platform to recapitulate organs in a dish. Hence, the organoid approach provides a more realistic drug response in comparison to the traditional 2D cellular models, which lack key physiological relevance due to the absence of proper surface topography and cellular interactions. Furthermore, an adverse outcome pathway (AOPs) provides a best fit model to identify various molecular and cellular events during the exposure of SARS-CoV-2. Hence, 3D organoid research provides information related to gene expression, cell behavior, antiviral studies and ACE2 expression in various organs. In this review, we discuss state-of-the-art lung, liver and kidney 3D organoid system utilizing the AOPs to study SARS-CoV-2 molecular pathogenesis. Furthermore, current challenges are discussed for future application of 3D organoid systems for various disease states.



中文翻译:

在 3D 类器官模型中研究 SARS-CoV-2 影响的不良结果方法

新型 SARS-CoV-2 病毒爆发是导致称为 COVID-19 的呼吸道疾病的主要原因。它已引起全球大流行,并导致数百万人死亡。主要的感染方式是呼吸系统疾病,但是,由于多器官并发症,COVID-19 患者的死亡率更高。由于 3Rs 原则(优化、减少、替换),科学界已将重点转移到 3D 类器官模型上,而不是测试动物模型。3D 类器官模型提供了更好的生理结构,因为它模拟了真实的组织微环境,是在培养皿中概括器官的最佳平台。因此,与传统的二维细胞模型相比,类器官方法提供了更真实的药物反应,由于缺乏适当的表面形貌和细胞相互作用,因此缺乏关键的生理相关性。此外,不利结果途径 (AOP) 提供了一个最佳拟合模型,用于识别 SARS-CoV-2 暴露期间的各种分子和细胞事件。因此,3D 类器官研究提供了与基因表达、细胞行为、抗病毒研究和各种器官中 ACE2 表达相关的信息。在这篇综述中,我们讨论了利用 AOP 研究 SARS-CoV-2 分子发病机制的最先进的肺、肝和肾 3D 类器官系统。此外,还讨论了未来将 3D 类器官系统应用于各种疾病状态的当前挑战。不良结果通路 (AOPs) 提供了一个最佳拟合模型来识别 SARS-CoV-2 暴露期间的各种分子和细胞事件。因此,3D 类器官研究提供了与基因表达、细胞行为、抗病毒研究和各种器官中 ACE2 表达相关的信息。在这篇综述中,我们讨论了利用 AOP 研究 SARS-CoV-2 分子发病机制的最先进的肺、肝和肾 3D 类器官系统。此外,还讨论了未来将 3D 类器官系统应用于各种疾病状态的当前挑战。不良结果通路 (AOPs) 提供了一个最佳拟合模型来识别 SARS-CoV-2 暴露期间的各种分子和细胞事件。因此,3D 类器官研究提供了与基因表达、细胞行为、抗病毒研究和各种器官中 ACE2 表达相关的信息。在这篇综述中,我们讨论了利用 AOP 研究 SARS-CoV-2 分子发病机制的最先进的肺、肝和肾 3D 类器官系统。此外,还讨论了未来将 3D 类器官系统应用于各种疾病状态的当前挑战。利用 AOP 研究 SARS-CoV-2 分子发病机制的肝肾 3D 类器官系统。此外,还讨论了未来将 3D 类器官系统应用于各种疾病状态的当前挑战。利用 AOP 研究 SARS-CoV-2 分子发病机制的肝肾 3D 类器官系统。此外,还讨论了未来将 3D 类器官系统应用于各种疾病状态的当前挑战。

更新日期:2021-08-23
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