Center on Advanced Studies and Technology (CAST), Department of Medical, Oral and Biotechnological Sciences, "G. d'Annunzio" University of Chieti-Pescara, 66100 Chieti, Italy.
Xellar Biosystems Inc., Cambridge, MA 02138, USA.
Int J Mol Sci. 2022 Sep 3;23(17):10071. doi: 10.3390/ijms231710071.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing the coronavirus disease 2019 (COVID-19), has provoked more than six million deaths worldwide and continues to pose a major threat to global health. Enormous efforts have been made by researchers around the world to elucidate COVID-19 pathophysiology, design efficacious therapy and develop new vaccines to control the pandemic. To this end, experimental models are essential. While animal models and conventional cell cultures have been widely utilized during these research endeavors, they often do not adequately reflect the human responses to SARS-CoV-2 infection. Therefore, models that emulate with high fidelity the SARS-CoV-2 infection in human organs are needed for discovering new antiviral drugs and vaccines against COVID-19. Three-dimensional (3D) cell cultures, such as lung organoids and bioengineered organs-on-chips, are emerging as crucial tools for research on respiratory diseases. The lung airway, small airway and alveolus organ chips have been successfully used for studies on lung response to infection by various pathogens, including corona and influenza A viruses. In this review, we provide an overview of these new tools and their use in studies on COVID-19 pathogenesis and drug testing. We also discuss the limitations of the existing models and indicate some improvements for their use in research against COVID-19 as well as future emerging epidemics.
严重急性呼吸综合征冠状病毒 2（SARS-CoV-2），引起 2019 年冠状病毒病（COVID-19），已在全球范围内导致超过 600 万人死亡，并继续对全球健康构成重大威胁。世界各地的研究人员为阐明 COVID-19 病理生理学、设计有效疗法和开发新疫苗以控制大流行做出了巨大努力。为此，实验模型是必不可少的。虽然动物模型和常规细胞培养在这些研究工作中被广泛应用，但它们通常不能充分反映人类对 SARS-CoV-2 感染的反应。因此，需要能够高度模拟 SARS-CoV-2 在人体器官中感染的模型，以发现针对 COVID-19 的新抗病毒药物和疫苗。三维（3D）细胞培养物，如肺类器官和生物工程器官芯片，正在成为呼吸道疾病研究的重要工具。肺气道、小气道和肺泡器官芯片已成功用于研究各种病原体（包括冠状病毒和流感 A 病毒）感染对肺的反应。在这篇综述中，我们概述了这些新工具及其在 COVID-19 发病机制和药物测试研究中的应用。我们还讨论了现有模型的局限性，并指出了一些改进方法，以便将其用于针对 COVID-19 的研究以及未来的新兴传染病。
