Precision-Cut Lung Slices in Pulmonary Physiology and Toxicology

Precision-cut lung slices (PCLS) are thin, uniformly sectioned ex vivo preparations of lung tissue that preserve the native three-dimensional architecture, multicellular composition and extracellular matrix of the respiratory organ. By maintaining intact alveolar units, airway branches and small blood vessels, PCLS provide a versatile platform for the quantitative analysis of airway mechanics, parenchymal biomechanics, inflammatory signalling and cellular toxicity. In pulmonary physiology, PCLS enable real-time imaging of bronchoconstriction, measurement of airway smooth muscle responses and mapping of regional strains in both large and small airways under controlled experimental conditions. In toxicological research, PCLS allow assessment of inhaled agents—such as particulate matter, smoke condensates or chemical irritants—on epithelial integrity, inflammatory mediator release and long-term viability. The model bridges the gap between simplified cell cultures and whole-animal studies, offering improved translational relevance, reduction in animal use and direct application to human-derived tissues. PCLS have underpinned investigations into disease mechanisms in asthma, chronic obstructive pulmonary disease and acute lung injury, and serve as a testbed for novel therapeutics, biological agents and environmental hazard evaluation.

Research from Nature Portfolio

Recent work has advanced the use of PCLS for chronic disease modelling by preserving airway smooth muscle contractility over extended culture periods. By supplementing standard medium with insulin, investigators maintained expression of essential contractile proteins in mouse slices for up to two weeks without compromising viability or tissue structure. This extension of functional lifespan enables repeated dosing studies, long-term exposure to cytokines such as interleukin-13 and sustained measurement of airway hyperresponsiveness. The approach opens new avenues for modelling prolonged inflammatory states and evaluating novel interventions aimed at reversing airway remodelling and dysfunction in chronic respiratory disorders.

Precision-Cut Lung Slices in Pulmonary Physiology and Toxicology publication trend

The graph below shows the total number of articles in precision-cut lung slices in pulmonary physiology and toxicology across all publications each year (not limited to Nature Index journals).

Technical terms

Precision-cut lung slices (PCLS): Ex vivo thin sections of lung tissue retaining native architecture and cellular heterogeneity.

Bronchoconstriction: Narrowing of airways due to airway smooth muscle contraction, measurable in PCLS by video-microscopy.

Airway hyperresponsiveness (AHR): Exaggerated constrictive response of airways to pharmacological or environmental stimuli.

Parenchyma: Functional lung tissue comprising alveoli and supporting interstitial structures, distinct from airways and vessels.

Ex vivo: Experimental approach conducted on organs or tissues maintained outside the living organism under controlled conditions.

Organotypic culture: Culture system preserving three-dimensional tissue architecture and cell–cell interactions to emulate in vivo functionality.

References

1. Landscape fire smoke airway exposure impairs respiratory and cardiac function and worsens experimental asthma. Journal of Allergy and Clinical Immunology (2024).
2. Precision cut lung slices: an innovative tool for lung transplant research. Frontiers in Immunology (2024).
3. Precision cut lung slices: an integrated ex vivo model for studying lung physiology, pharmacology, disease pathogenesis and drug discovery. Respiratory Research (2024).
4. Airway and Parenchymal Strains during Bronchoconstriction in the Precision Cut Lung Slice. Frontiers in Physiology (2016).
5. Preserving Airway Smooth Muscle Contraction in Precision-Cut Lung Slices. Scientific Reports (2020).