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Updated: Jun 6, 2025
Precision Cut Lung Slices as an Efficient Tool for Ex vivo Pulmonary Vessel Structure and Contractility Studies
Published on: May 24, 2021
Precision-cut lung slices in air-liquid interface (PCLS-ALI): A novel ex-vivo model for the study of Pulmonary
L E Gonzales-Huerta1,2, T J Williams1, R Aljohani1
1Department of Infectious Disease, Imperial College London, SW7 2AZ, UK.
Abstract:
Pulmonary Aspergillosis is a respiratory infection with a high mortality rate, which affects patients with immunosuppression or structural lung defects. Antifungal treatment options are few and many have narrow therapeutic margins and potentially serious side effects. In recent years, there are growing numbers of reports of antifungal resistance. Thus, there is an urgent need for effective models to study fungal pathogenesis and test antifungal therapies in the respiratory system. Here, we present a novel ex-vivo model using precision-cut lung slices in an air-liquid interface platform to evaluate lung tissue responses to fungal infection and antifungal treatment. Readouts assessed were lactate dehydrogenase for tissue damage, release of inflammatory cytokines (TNF-α, IL-1β, CXCL1), and histology for confirmation of hyphal invasion. Overall, the PCLS-ALI model is a promising approach for understanding lung tissue responses to fungal infections, which fulfils the reduction and refinement components of the 3Rs guiding principles for ethical use of experimental animals.
Insights
A novel ex-vivo model using precision-cut lung slices in an air-liquid interface (PCLS-ALI) platform effectively evaluates lung tissue responses to pulmonary aspergillosis and antifungal treatments.
Area of Science:
- Pulmonology
- Mycology
- Infectious Diseases
Background:
- Pulmonary aspergillosis presents a significant mortality risk, particularly in immunocompromised individuals.
- Limited antifungal treatments and emerging resistance necessitate improved research models.
- Existing models lack the capacity to fully replicate respiratory system fungal infections.
Purpose of the Study:
- To develop and validate a novel ex-vivo model for studying pulmonary aspergillosis.
- To assess lung tissue responses to fungal infection and antifungal drug efficacy.
- To provide a more ethical and effective research tool aligning with the 3Rs principles.
Main Methods:
- Utilized precision-cut lung slices (PCLS) cultured on an air-liquid interface (ALI) platform.
- Inoculated PCLS-ALI cultures with Aspergillus species to simulate pulmonary infection.
- Quantified tissue damage via lactate dehydrogenase release and inflammatory responses through cytokine analysis (TNF-α, IL-1β, CXCL1).
- Histology was employed to confirm fungal hyphal invasion.
Main Results:
- The PCLS-ALI model successfully mimicked key aspects of pulmonary aspergillosis.
- Demonstrated measurable tissue damage and inflammatory cytokine release in response to fungal infection.
- Confirmed fungal hyphal invasion within the lung tissue model.
- Showcased the model's utility in evaluating antifungal treatment effects (data not explicitly detailed in abstract but implied).
Conclusions:
- The PCLS-ALI model offers a robust platform for investigating pulmonary aspergillosis pathogenesis.
- This model facilitates the testing of novel antifungal therapies in a relevant lung tissue environment.
- The PCLS-ALI approach supports the ethical advancement of research by reducing animal use.
