Precision-cut lung slices

Studying early events in the pathogenesis of respiratory diseases in human lung tissue

For improved prediction of chemical toxicity and adverse drug reactions as well as for safety assessment in line with the principle of the 3Rs, other models than animals are needed. The aim of the 3Rs principle is to avoid animal experiments altogether (replacement), to reduce the number of animals per experiment (reduction) and to keep animal distress to an absolute minimum (refinement). As an adverse outcome induced by an agent (such as a chemical or drug) can be linked to molecular initiation events, it is possible to investigate early events in the pathogenesis of acute and chronic respiratory diseases by measurement of key events at the cellular or tissue level.

© Fraunhofer ITEM, Ralf Mohr
Precision-cut lung slices (PCLS for short) can be exposed to chemicals, proteins or complex mixtures such as cigarette smoke at the air-liquid interface.

Human lung tissue is complex, it contains many different cell types and resident immune cells. As a result, injuries are often associated not only with increased release of intracellular enzymes but also with release of pro-inflammatory cytokines and chemokines such as TNF-α, IL-1β and others that serve as markers, for example of inflammation and fibrosis. Fraunhofer ITEM receives human lung tissue from two hospitals in Hannover and ensures the high quality of these samples through a standardized approach to tissue collection and appropriate quality controls. From these lung tissue samples, the Fraunhofer ITEM researchers prepare precision-cut lung slices (PCLS), which can subsequently be exposed to different test items, either in submersion culture or at the air-liquid interface. The combination of different techniques as well as the use of both healthy and end-stage diseased tissue enables the identification of chemical-changed biomarkers and pathways.

Over the past years, Fraunhofer ITEM scientists have built up expertise to advance the discovery and safety of drugs and chemicals by the use of human tissue. First publications on this topic defined a new standardized approach for using lung tissue ex vivo to assess lung injury and inflammation. This approach was then used to develop disease-related models of asthma, COPD, fibrosis and infection. By using these disease models, it was possible to show for example how pharmaceutical immunosuppression can lead to an increased risk for infection with influenza. In this context, human lung tissue increases the predictive validity of disease models and provides a reference point that can be correlated with clinical symptoms. Nevertheless, integrating human tissue into research and development remains a significant challenge.

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About 5 percent of all Germans suffer from asthma. No wonder that scientists are searching for new drugs to alleviate their suffering. Unfortunately, animal testing is currently the only means to find out if a chemical causes allergies. Fraunhofer ITEM is now working on an animal-friendly alternative.


Katherina Sewald

Contact Press / Media

Dr. Katherina Sewald

Head of Department of Preclinical Pharmacology and In-vitro Toxicology

Phone +49 511 5350-323