Viral infection model in precision-cut lung slices


Viral infection model in precision-cut lung slices (human, mouse)

HRV is the most common pathogen to induce respiratory infection in adults leading not only to simple common cold but also to severe exacerbations in patients with chronic lung disease (e.g. asthma).

Precision-cut lung slices, which are viable lung slices generated e.g. from human lung, are an ex vivo organotypic tissue model which is valuable as translational model bridging the gap between experimental animal research and clinical application. PCLS are used to study a wide range of endpoints e.g. cytotoxicity, cytokine release, bronchoconstriction.

We are currently developing a viral infection model in human and mouse PCLS using HRV, which aims to evaluate viral infection and anti-viral immune response particularly with aim of species comparison.

Species

Human, Mouse, others possible

Fields of application

  • preclinical efficacy testing
  • preclinical safety testing (cytotoxicity)

Endpoints/Outcome parameter

  • Viral respiratory infection
  • anti-viral immune response
  • species comparison

Readout parameter

  • Viral replication (TCID50 assay, confocal microscopy)
  • Cytokine profiles (ELISA, MSD)
  • Histology: conventional staining and tissue pathohistology/conventional microscopy  immunohistochemistry/ fluorescence microscopy/ confocal microscopy (e.g. for detection of targets e.g. receptor expression, virus localization)
  • Lung tissue analysis (RNA isolation/ gene expression, cytokine profiles,…)

Quality management and validation

  • Internal quality management
  • Historical data available
  • Reference compounds e.g. dexamethasone, roflumilast
  • Performance under GLP possible

References

  • The HRV1b PCLS infection model was developed under the frame oft he U-BIOPRED project.