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

Area of Science:

• Respiratory Virology
• Cell Biology
• Regenerative Medicine

Background:

• Development of in vitro models is crucial for studying severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
• Existing models may not fully recapitulate the complex airway environment for efficient viral infection studies.

Purpose of the Study:

• To develop and characterize an advanced in vitro cell model for SARS-CoV-2 research.
• To compare infection efficiency between bronchial organoids (BO) and a derived air-liquid interface model (BO-ALI).
• To investigate cellular responses and regeneration mechanisms following SARS-CoV-2 infection.

Main Methods:

• Infection experiments were performed using eight SARS-CoV-2 variants in BO and BO-ALI models.
• Cellular tropism and viability were assessed post-infection.
• Mechanisms of airway epithelial regeneration were investigated, including the role of fibroblast growth factor 10 (FGF10) signaling.

Main Results:

• The BO-ALI model demonstrated over 1,000 times higher infection efficiency compared to the BO model.
• SARS-CoV-2 primarily infected ciliated cells, leading to their death, while basal cells remained uninfected.
• Surviving basal cells differentiated into ciliated cells, a process dependent on FGF10 signaling.

Conclusions:

• The BO-ALI model serves as a robust platform for evaluating SARS-CoV-2 infection and COVID-19 therapeutic agents.
• This model also offers valuable insights into airway regeneration processes following viral damage.
• Findings highlight the potential of BO and BO-ALI in advancing respiratory virus research and regenerative medicine.