Generation of human bronchial organoids for SARS-CoV-2 research

Authors: Suzuki et al.

Link to paper: https://doi.org/10.1101/2020.05.25.115600

Journal/ Pre-Print: bioRxiv

Tags: Infection model, organoids, Immunology/Immunity, Drug repurpose

Research Highlights 

1. Generation of human bronchial organoids (hBOs) from cryopreserved adult human bronchial epithelial cells (hBEpC), which show higher base line expression of ACE2 and TMPRSS2 compared to hBEpC

2. Use of hBO as a model to study viral infection and its close resemblance to 2D airway cultures

3. SARS-CoV2 productively infects hBOs to induce Type I IFN response and ISGs, treatment of hBOs with camostat decreased viral replication and infectious virus release

Summary 

The study describes the generation of human bronchial organoids (hBOs) from cryopreserved adult human bronchial epithelial cells. The authors show that hBOs contain basal, club, ciliated, and goblet cells and SARS-CoV2 can infect and replicate in the cells. They also demonstrate that these hBOs can be applied for drug discovery studies by showing Camostat suppresses viral replication. Localised infection of SARS-CoV2 of basal cells induces a Type I IFN response and ISGs expression. Overall, this study adds on to existing studies of efficiently using 3D cell culture models to study host-pathogen interactions.

Impact for SARS-CoV2/COVID19 research efforts

 Understand the immune response to SARS-CoV2/COVID19 in bronchial epithelial cells

Understand the virology and/or cell biology of SARS-CoV2/COVID19

Develop diagnostic tools for SARS-CoV2/COVID19

Inhibit of SARS-CoV2/COVID19 transmission

Treat of SARS-CoV2/COVID19 positive individuals

Study Type

· In silico study / bioinformatics study

· In vitro study/ ex vivo study

Strengths and limitations of the paper

Novelty: Generation of hBOs from cryopreserved cells

Standing in the field: RNA sequencing data shows that SARS-Cov2 infected bronchial cells induce an interferon gene signature and 3D cell culture models provide an efficient tool to study the virus. This supports existing evidence where gut, vascular and kidney organoids have been used as an infection model and were also shown to induce an interferon response upon viral infection

Appropriate statistics: Yes

Viral model used: SARS-CoV-2/Hu/DP/Kng/19-020 – Japanese Strain

Translatability: The use of hBOs to study drug-interactions makes it an attractive and a viable tool with translational potential. More data and experimental replicates are needed to verify data.

Main limitations:

- The paper only provides a descriptive framework of using hBOs as a tool to study viral infection

- The study does not present any additional data about viral entry and replication in bronchial epithelial cells and adds on to existing literature that SARS-CoV2 induces a strong interferon response upon infection

- The therapeutic efficacy of Camostat at different concentrations along with other recommended drugs could have been explored.