Human iPS cell-derived respiratory organoids as a model for respiratory syncytial virus infection

Rina Hashimoto1,2, Yukio Watanabe1, Abeer Keshta1

  • 1Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.

Life Science Alliance
|April 22, 2025
PubMed

Insights

Human respiratory organoids offer a better model for studying respiratory syncytial virus (RSV) infection than traditional cell cultures. This advanced model accurately reflects RSV pathophysiology and aids in evaluating potential treatments.

Area of Science:

  • Virology
  • Stem Cell Biology
  • Respiratory Medicine

Background:

  • Respiratory syncytial virus (RSV) causes significant disease in young children, but its pathophysiology is poorly understood.
  • Current cell models, like HEp-2, do not fully replicate the human respiratory system's response to RSV.
  • Advanced models are crucial for effective RSV research and therapeutic development.

Purpose of the Study:

  • To evaluate human-induced pluripotent stem cell-derived respiratory organoids as a model for RSV infection.
  • To assess the utility of these organoids in pharmaceutical research for RSV.
  • To compare organoid response to RSV with existing cell culture models.

Main Methods:

  • Human-induced pluripotent stem cell-derived respiratory organoids were infected with RSV.
  • Viral genome and protein expression, tissue damage, and cytokine levels were analyzed.
  • The efficacy of monoclonal antibodies and ribavirin against RSV in organoids was tested.

Main Results:

  • RSV-infected organoids showed high viral replication, epithelial damage, and increased collagen.
  • Pro-inflammatory cytokine levels elevated post-RSV infection in organoids.
  • Monoclonal antibodies effectively inhibited RSV infection, while ribavirin had limited impact.

Conclusions:

  • Respiratory organoids provide a more accurate model for studying RSV infection and human host response.
  • These organoids are valuable tools for pharmaceutical research and the development of RSV therapeutics.
  • The findings support the use of organoids for advancing RSV understanding and treatment strategies.