1. Academic Validation
  2. Cell response analysis in SARS-CoV-2 infected bronchial organoids

Cell response analysis in SARS-CoV-2 infected bronchial organoids

  • Commun Biol. 2022 May 30;5(1):516. doi: 10.1038/s42003-022-03499-2.
Emi Sano  # 1 Tatsuya Suzuki  # 2 Rina Hashimoto  # 1 Yumi Itoh 2 Ayaka Sakamoto 1 Yusuke Sakai 3 Akatsuki Saito 4 Daisuke Okuzaki 5 6 7 Daisuke Motooka 5 Yukiko Muramoto 8 Takeshi Noda 8 Tomohiko Takasaki 9 Jun-Ichi Sakuragi 9 Shohei Minami 10 Takeshi Kobayashi 10 Takuya Yamamoto 1 11 12 13 Yasufumi Matsumura 14 Miki Nagao 14 Toru Okamoto 15 Kazuo Takayama 16 17
Affiliations

Affiliations

  • 1 Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, 606-8507, Japan.
  • 2 Institute for Advanced Co-Creation Studies, Research Institute for Microbial Diseases, Osaka University, Suita, 565-0871, Japan.
  • 3 Laboratory of Veterinary Pathology, Joint Faculty of Veterinary Medicine, Yamaguchi University, Yamaguchi, 753-8511, Japan.
  • 4 Department of Veterinary Science, Faculty of Agriculture, University of Miyazaki, Miyazaki, 889-2192, Japan.
  • 5 Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Suita, 565-0871, Japan.
  • 6 Single Cell Genomics, Human Immunology, WPI Immunology Frontier Research Center, Osaka University, Suita, 565-0871, Japan.
  • 7 Institute for Open and Transdisciplinary Research Initiatives, Osaka University, Suita, 565-0871, Japan.
  • 8 Laboratory of Ultrastructural Virology, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, 606-8507, Japan.
  • 9 Kanagawa Prefectural Institute of Public Health, Chigasaki, Kanagawa, 253-0087, Japan.
  • 10 Laboratory of Viral Replication, International Research Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, 565-0871, Japan.
  • 11 Institute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto University, Kyoto, 606-8501, Japan.
  • 12 Medical-risk Avoidance based on iPS Cells Team, RIKEN Center for Advanced Intelligence Project (AIP), Kyoto, 606-8507, Japan.
  • 13 AMED-CREST, Japan Agency for Medical Research and Development (AMED), Tokyo, 100-0004, Japan.
  • 14 Department of Clinical Laboratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, 606-8303, Japan.
  • 15 Institute for Advanced Co-Creation Studies, Research Institute for Microbial Diseases, Osaka University, Suita, 565-0871, Japan. [email protected].
  • 16 Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, 606-8507, Japan. [email protected].
  • 17 AMED-CREST, Japan Agency for Medical Research and Development (AMED), Tokyo, 100-0004, Japan. [email protected].
  • # Contributed equally.
Abstract

The development of an in vitro cell model that can be used to study severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) research is expected. Here we conducted Infection experiments in bronchial organoids (BO) and an BO-derived air-liquid interface model (BO-ALI) using 8 SARS-CoV-2 variants. The Infection efficiency in BO-ALI was more than 1,000 times higher than that in BO. Among the bronchial epithelial cells, we found that ciliated cells were infected with the virus, but basal cells were not. Ciliated cells died 7 days after the viral Infection, but basal cells survived after the viral Infection and differentiated into ciliated cells. Fibroblast Growth Factor 10 signaling was essential for this differentiation. These results indicate that BO and BO-ALI may be used not only to evaluate the cell response to SARS-CoV-2 and coronavirus disease 2019 (COVID-19) therapeutic agents, but also for airway regeneration studies.

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