Mice refinement: from invasive intratracheal instillation to intubation for lung fibrosis studies

Background

In our laboratory, we are using the intratracheal instillation of chemicals (FITC and Bleomycin) or particles (e.g, asbestos and silica dust) to induce lung fibrosis or lung inflammation in mice. This procedure is a well-known surgical act, used by the majority of researcher in the field, involving a skin incision of the skin to expose the trachea and followed by the insertion of a needle into the trachea for the delivery of compounds.

With the support of the Animal Welfare Officer (AWO) at the UNIFR and the strong recommendations by the cantonal authority of Fribourg, we decide to refine the current technique that will be implemented to our future projects. We have two projects, that have been submitted to the cantonal authority and fro research grant at the Swiss National Foundation which aims to compare intratracheal instillation and intubation for comparison with age, sex, and response to treatments.

Aim

University of Fribourg -> University of Zurich

We want to learn the intubation technique to refine the current intratracheal instillation surgery technique. Intubation is used in several rodent models, to study lung physiological and pathological models. Intubation has been is along-established technique extensively performed in rats. Even if intubation has been used in mouse, the technical difficulties encountered by researchers to develop this method induced persistence in the use of intratracheal instillation technique.

For several reasons the intubation technique would be more suitable for us for the induction of lung fibrosis. Indeed, lung fibrosis is developing due to the repeated exposure to chemicals or physicals agents. Intratracheal instillation can not reproduce this important parameter as it can not be performed several times on the same animal. We are expecting that multiple low doses exposures using intubation will lead to the development of lung fibrosis in a more consistent and reproducible way relative to the human pathology.

Especially, our current project aimed to compare in vivo models (e.g., intratracheal instillation and intubation (once vs multiple exposure)) with in vitro (patients derived cells and primary cells) and Lung-On-Chip models (Alveolix, Bern) as potential alternatives for drugs characterizations. We are comparing clinical standard of care, drugs that failed in human clinical trials, and new promizing candidates by using these models to define which models are accurate for drugs efficacy and safety studies and can be translated to human conditions and use in clinic for drugs candidate. The overall aim would be to replace in vivo models with in vitro (patients derived cells and primary cells) and/or Lung-On-Chip models (Alveolix, Bern).