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

Literature Information ​

DOI10.1038/s41592-022-01453-y
PMID35396481
JournalNature methods
Impact Factor32.1
JCR QuartileQ1
Publication Year2022
Times Cited67
Keywordshuman organoids, SARS-CoV-2, COVID-19, immune response, drug discovery
Literature TypeJournal 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
Pages418-428
Issue19(4)
AuthorsYuling Han, Liuliu Yang, Lauretta A Lacko, Shuibing Chen

TL;DR ​

This Perspective highlights the use of organoids derived from human pluripotent stem cells and adults to investigate the tropism of SARS-CoV-2, the host immune response, and facilitate drug discovery and vaccine development in the context of COVID-19. It discusses current methodologies, challenges faced in organoid-based research, and future directions for studying SARS-CoV-2 and other emerging viruses, underscoring the significance of organoid models in understanding viral pathogenesis.

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human organoids · SARS-CoV-2 · COVID-19 · immune response · drug discovery

Abstract ​

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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Primary Questions Addressed ​

  1. How do different types of organoids compare in their effectiveness for modeling SARS-CoV-2 infection?
  2. What specific physiological responses have been observed in organoids when exposed to SARS-CoV-2?
  3. In what ways can organoid models contribute to understanding the long-term effects of COVID-19 on various organs?
  4. What advancements in technology are necessary to enhance the use of organoids in drug discovery for COVID-19?
  5. How can the insights gained from organoid studies inform vaccine development strategies against SARS-CoV-2?

Key Findings ​

Key Insights ​

  1. Research Background and Objectives: The COVID-19 pandemic, caused by SARS-CoV-2, has emerged as one of the most lethal public health crises in recent history, impacting not only the respiratory system but also multiple organ systems. The objective of the research is to utilize human organoid models—derived from pluripotent stem cells and adult tissues—to better understand SARS-CoV-2 infection dynamics, including viral tropism, host immune responses, and the resultant organ damage. This approach aims to provide insights into the pathophysiology of COVID-19 and facilitate drug discovery and vaccine development.

  2. Main Methods and Findings: The study reviews advancements in the use of organoids, which are three-dimensional cultures that mimic the physiological characteristics of organs, for modeling SARS-CoV-2 infections. Both human pluripotent stem cell-derived organoids and adult organoids have been employed to explore how the virus interacts with different cell types, the host's immune response, and the mechanisms behind organ damage. The findings reveal that organoids can effectively replicate the infection process, allowing researchers to observe the effects of SARS-CoV-2 at a cellular level and to identify potential therapeutic interventions.

  3. Core Conclusions: The research highlights that organoid models are indispensable tools for studying SARS-CoV-2 due to their ability to closely resemble human organ physiology and pathology. They facilitate a deeper understanding of the virus's tropism and the complex interplay between the virus and the host's immune system. Additionally, these models present opportunities for screening antiviral drugs and testing vaccine candidates, thereby accelerating the development of effective treatments and preventive measures against COVID-19 and similar emerging viruses.

  4. Research Significance and Impact: The application of organoid technology in COVID-19 research represents a significant advancement in infectious disease modeling, providing a platform for personalized medicine approaches. By overcoming limitations associated with traditional cell culture systems and animal models, organoids offer a more accurate representation of human disease mechanisms. The insights gained from this research are crucial not only for combating the current pandemic but also for preparing for future viral outbreaks, highlighting the potential of organoids in infectious disease research and therapeutic development. This work underscores the importance of innovative modeling techniques in enhancing our understanding of viral pathogenesis and improving public health responses.

References ​

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  2. Modeling Development and Disease with Organoids. - Hans Clevers - Cell (2016)
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Literatures Citing This Work ​

  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 more literatures)

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