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June 02, 2022

COVID-19 research using bronchial organoids and drug discovery applications

The group led by Dr. Kazuo Takayama developed two in vitro models to study SARS-CoV-2, a bronchial organoids model (BO) and a BO-derived air-liquid interface model (BO-ALI), and showed that they can be used for drug screening for infectious diseases including COVID-19.

An in vitro lung model that faithfully reproduces the human respiratory organ is essential for conducting COVID-19 drug screening. BO and alveolar organoids are excellent tools for faithfully mimicking the human respiratory organ and are expected to be applied to COVID-19 research.

In this study, the research team developed two human bronchial models, BO and BO-ALI. SARS-CoV-2 infection experiments confirmed that the infection efficiency in BO-ALI was more than 2,000 times higher than that in BO. The researchers confirmed the anti-viral effect of therapeutic agents such as remdesivir, molnupiravir, and camostat, using BO-ALI. Comparative analyses of eight SARS-CoV-2 variants, including the omicron strain, showed that the infection efficiency in BO-ALI of the Omicron was slightly lower than those of the other variants.

Next, in attempting to identify the cells that SARS-CoV-2 infects, the researchers found that the virus efficiently infects ciliated cells but rarely infects basal cells. They also discovered that nearly all ciliated cells died subsequently whereas basal cells survived and differentiated into bronchial epithelial cells, including ciliated cells. The regenerative capacity of basal cells was dependent on fibroblast growth factor 10 (FGF10).

These findings suggest that BO-ALI produced from BO can be used to evaluate COVID-19 therapeutics, analyze SARS-CoV-2 variants, and study bronchial tissue regeneration.

The results of this study were published online in Communications Biology on May 30, 2022.

Paper Details

Journal: Communications Biology
Title: Cell response analysis in SARS-CoV-2 infected bronchial organoids
Authors: Emi Sano^1**, Tatsuya Suzuki^2**, Rina Hashimoto^1**, Yumi Itoh², Ayaka Sakamoto¹, Yusuke Sakai³, Akatsuki Saito⁴, Daisuke Okuzaki^5,6,7, Daisuke Motooka⁵, Yukiko Muramoto⁸, Takeshi Noda⁸, Tomohiko Takasaki⁹, Jun-Ichi Sakuragi⁹, Shohei Minami¹⁰, Takeshi Kobayashi¹⁰, Takuya Yamamoto^1,11,12,13, Yasufumi Matsumura¹⁴, Miki Nagao¹⁴, Toru Okamoto^2*, Kazuo Takayama^1,13*
*：Corresponding authors
**：Co-first authors (These authors contributed equally.)
Author Affiliations:
1. Center for iPS Cell Research and Application (CiRA), Kyoto University
2. Institute for Advanced Co-Creation Studies, Research Institute for Microbial Diseases, Osaka University
3. Laboratory of Veterinary Pathology, Joint Faculty of Veterinary Medicine, Yamaguchi University
4. Department of Veterinary Science, Faculty of Agriculture, University of Miyazaki
5. Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University
6. Single Cell Genomics, Human Immunology, WPI Immunology Frontier Research Center, Osaka University
7. Institute for Open and Transdisciplinary Research Initiatives, Osaka University
8. Laboratory of Ultrastructural Virology, Institute for Frontier Life and Medical Sciences, Kyoto University
9. Kanagawa Prefectural Institute of Public Health
10. Laboratory of Viral Replication, International Research Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University
11. Institute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto University
12. Medical-risk Avoidance based on iPS Cells Team, RIKEN Center for Advanced Intelligence Project (AIP)
13. AMED-CREST, Japan Agency for Medical Research and Development (AMED)
14. Department of Clinical Laboratory Medicine, Graduate School of Medicine, Kyoto University

doi: 10.1038/s42003-022-03499-2