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Human organoid models to study SARS-CoV-2 infection. ​

文献信息 ​

DOI10.1038/s41592-022-01453-y
PMID35396481
期刊Nature methods
影响因子32.1
JCR 分区Q1
发表年份2022
被引次数67
关键词器官类器官, SARS-CoV-2, COVID-19, 免疫反应, 药物发现
文献类型Journal Article, Review, Research Support, U.S. Gov't, Non-P.H.S., Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
ISSN1548-7091
页码418-428
期号19(4)
作者Yuling Han, Liuliu Yang, Lauretta A Lacko, Shuibing Chen

一句话小结 ​

本篇展望探讨了类器官在研究SARS-CoV-2感染机制、宿主反应及免疫损伤中的应用，强调了其在药物发现和疫苗开发中的潜力。研究指出，尽管类器官模型在COVID-19研究中展现出显著价值，但仍面临技术挑战，未来需要进一步探索其在新兴病毒研究中的应用。

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器官类器官 · SARS-CoV-2 · COVID-19 · 免疫反应 · 药物发现

摘要 ​

2019冠状病毒病（COVID-19）是由严重急性呼吸综合症冠状病毒2型（SARS-CoV-2）引起的，它是历史上最致命的流行病之一。SARS-CoV-2不仅感染呼吸道，还会对多个器官造成损害。类器官作为能够自我更新并重现不同器官各种生理功能的强大平台，为COVID-19建模提供了有效的工具。在本篇展望中，我们概述了当前利用人类多能干细胞衍生的类器官和成人类器官类器官研究SARS-CoV-2嗜性、宿主反应及免疫细胞介导的宿主损伤的努力，以及药物发现和疫苗开发的相关工作。我们总结了在基于类器官的COVID-19研究中使用的技术，讨论了仍然存在的挑战，并提供了未来在类器官模型应用于研究SARS-CoV-2及未来新兴病毒方面的展望。

英文摘要 ​

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is one of the deadliest pandemics in history. SARS-CoV-2 not only infects the respiratory tract, but also causes damage to many organs. Organoids, which can self-renew and recapitulate the various physiology of different organs, serve as powerful platforms to model COVID-19. In this Perspective, we overview the current effort to apply both human pluripotent stem cell-derived organoids and adult organoids to study SARS-CoV-2 tropism, host response and immune cell-mediated host damage, and perform drug discovery and vaccine development. We summarize the technologies used in organoid-based COVID-19 research, discuss the remaining challenges and provide future perspectives in the application of organoid models to study SARS-CoV-2 and future emerging viruses.

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主要研究问题 ​

  1. 在使用人类类器官模型研究SARS-CoV-2感染时，哪些特定的器官模型被认为是最有效的？
  2. 目前在类器官研究中，有哪些新兴技术能够提高对SARS-CoV-2感染机制的理解？
  3. 通过类器官模型，如何评估不同药物对SARS-CoV-2的疗效及其潜在的副作用？
  4. 在类器官模型中，如何模拟宿主的免疫反应以研究SARS-CoV-2引起的免疫损伤？
  5. 针对未来新兴病毒，类器官模型的研究方向和应用前景是什么？

核心洞察 ​

1. 研究背景和目的 ​

新冠肺炎（COVID-19）由严重急性呼吸综合症冠状病毒2型（SARS-CoV-2）引起，是历史上最致命的疫情之一。该病毒不仅感染呼吸道，还对多脏器造成损害。研究者们亟需有效的模型来理解SARS-CoV-2的感染机制、宿主反应及免疫细胞介导的损伤。人类类器官（organoids）作为一种能够自我更新并模拟不同器官生理特征的强大平台，为研究COVID-19提供了有效的工具。此文旨在概述当前应用人类多能干细胞衍生类器官和成体类器官研究SARS-CoV-2感染的努力。

2. 主要方法和发现 ​

研究中总结了使用人类多能干细胞衍生类器官和成人类器官的多种技术，探索了SARS-CoV-2的嗜性（tropism）、宿主反应及免疫细胞介导的损伤。同时，研究者们也借助这些类器官进行药物发现和疫苗开发。通过构建类器官模型，研究能够模拟病毒在不同人类组织中的感染过程，进而深入了解病毒与宿主之间的相互作用。

3. 核心结论 ​

人类类器官模型为研究SARS-CoV-2提供了新的视角和方法，能够有效地模拟病毒感染对不同器官的影响。这些模型不仅有助于解析病毒的生物学特性，还为药物筛选和疫苗开发提供了有价值的实验平台。尽管当前的研究已经取得了一定进展，但仍面临技术挑战和模型优化的需求。

4. 研究意义和影响 ​

本研究的意义在于强调了类器官模型在COVID-19及未来新兴病毒研究中的潜力。这些模型可以提供更为真实的人体生理环境，能够帮助科研人员更准确地理解病毒感染机制、评估治疗效果，并推动新疗法的开发。同时，随着病毒变异和新病毒的出现，类器官技术将成为应对公共卫生危机的重要工具，为全球健康安全提供保障。

参考文献 ​

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  9. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. - Kazutoshi Takahashi;Shinya Yamanaka - Cell (2006)
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引用本文的文献 ​

  1. Advances of Engineered Hydrogel Organoids within the Stem Cell Field: A Systematic Review. - Zheng Li;Muxin Yue;Yunsong Liu;Ping Zhang;Jia Qing;Hao Liu;Yongsheng Zhou - Gels (Basel, Switzerland) (2022)
  2. 3D Human Organoids: The Next "Viral" Model for the Molecular Basis of Infectious Diseases. - Shirley Pei Shan Chia;Sharleen Li Ying Kong;Jeremy Kah Sheng Pang;Boon-Seng Soh - Biomedicines (2022)
  3. Better In Vitro Tools for Exploring Chlamydia trachomatis Pathogenesis. - Simone Filardo;Marisa Di Pietro;Rosa Sessa - Life (Basel, Switzerland) (2022)
  4. Three-Dimensional In Vitro Cell Culture Models for Efficient Drug Discovery: Progress So Far and Future Prospects. - Shaimaa M Badr-Eldin;Hibah M Aldawsari;Sabna Kotta;Pran Kishore Deb;Katharigatta N Venugopala - Pharmaceuticals (Basel, Switzerland) (2022)
  5. 3D Lung Tissue Models for Studies on SARS-CoV-2 Pathophysiology and Therapeutics. - Roberto Plebani;Haiqing Bai;Longlong Si;Jing Li;Chunhe Zhang;Mario Romano - International journal of molecular sciences (2022)
  6. Lung Organoids as Model to Study SARS-CoV-2 Infection. - Li Peng;Li Gao;Xinya Wu;Yuxin Fan;Meixiao Liu;Jingjing Chen;Jieqin Song;Jing Kong;Yan Dong;Bingxue Li;Aihua Liu;Fukai Bao - Cells (2022)
  7. Human early syncytiotrophoblasts are highly susceptible to SARS-CoV-2 infection. - Degong Ruan;Zi-Wei Ye;Shuofeng Yuan;Zhuoxuan Li;Weiyu Zhang;Chon Phin Ong;Kaiming Tang;Timothy Theodore Ka Ki Tam;Jilong Guo;Yiyi Xuan;Yunying Huang;Qingqing Zhang;Cheuk-Lun Lee;Liming Lu;Philip C N Chiu;William S B Yeung;Fang Liu;Dong-Yan Jin;Pentao Liu - Cell reports. Medicine (2022)
  8. Lung Organoids for Hazard Assessment of Nanomaterials. - Miriam T Kastlmeier;Eva M Guenther;Tobias Stoeger;Carola Voss - International journal of molecular sciences (2022)
  9. Potential long-term effects of SARS-CoV-2 infection on the pulmonary vasculature: Multilayered cross-talks in the setting of coinfections and comorbidities. - Rahul Kumar;Öznur Aktay-Cetin;Vaughn Craddock;Daniel Morales-Cano;Djuro Kosanovic;Angel Cogolludo;Francisco Perez-Vizcaino;Sergey Avdeev;Ashok Kumar;Anil Kumar Ram;Stuti Agarwal;Ananya Chakraborty;Rajkumar Savai;Vinicio de Jesus Perez;Brian B Graham;Ghazwan Butrous;Navneet K Dhillon - PLoS pathogens (2023)
  10. Mimicking the Biological Sense of Taste In Vitro Using a Taste Organoids-on-a-Chip System. - Jianguo Wu;Changming Chen;Chunlian Qin;Yihong Li;Nan Jiang;Qunchen Yuan;Yan Duan;Mengxue Liu;Xinwei Wei;Yiqun Yu;Liujing Zhuang;Ping Wang - Advanced science (Weinheim, Baden-Wurttemberg, Germany) (2023)

... (57 更多 篇文献)

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