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14 January 2025

Lung-on-Chip: A Humane Solution for Testing Lung Function and Toxicity

Human alveolar cells on a chip show promising characteristics – similar to those seen in studies using animals.

Researchers increasingly use models that use living cells outside of animals to study lung function, inhalation toxicity, drug safety, and disease mechanisms. However, creating reliable models of alveolar cells1, which are located deep in the airways, has been challenging.

A breakthrough has been made by a team led by 3RCC grant-recipient Olivier Guénat at the ARTORG Center2 in Bern. They successfully combined a human alveolar cell line with organ-on-chip technology to create a lung-on-chip model3. This innovative model mimics the lung environment with features such as breathing-like motions and ultrathin, porous, and elastic membranes. Published in the Journal of Frontiers in Toxicology, the lung-on-chip model shows great promise for replacing animal models in the study of lung function, disease, and treatment.

One of the key achievements of this model is addressing the need for a functional alveolar epithelial barrier—the layer that separates the external environment from the interior of the lungs. This barrier not only protects against environmental stressors and pathogens but also prevents fluid accumulation in the lungs. Combining organ-on-chip technology with human alveolar cells, the researchers used techniques like flow cytometry (which analyzes the properties of cells using lasers) and gene expression analyses (which assess whether genes are activated or deactivated in response to stimuli) to find that the cells matured into the specialized lung cells found in alveoli. This maturation was enhanced when exposed to a breathing cycle that physically stretched the cells.

The team confirmed that the cellular model exhibited features of cells sensitive to SARS-CoV2 infection, making it a useful model for studying how the virus infects human lungs and testing potential treatments, as it closely represents real human responses to the virus. Using measures of trans-barrier electrical resistance (a measure used to assess how well cells form a barrier), the researchers found that the lung-on-chip model displayed a tight and functional alveolar barrier, which could be disrupted using drugs that trigger fibrosis or inflammatory stimuli. Thus, the lung-on-chip model successfully mimics a healthy, intact alveolar barrier, which is crucial for proper lung function. By showing that this barrier can be disrupted with drugs that induce fibrosis (scarring) or inflammatory responses, the model becomes a powerful tool for studying diseases like pulmonary fibrosis or COVID-19, where the lung barrier is compromised. Researchers can use this model to test how various drugs or treatments impact lung function, potentially helping to develop therapies to protect or restore the barrier.

This new lung-on-chip model represents a significant advancement in the field, providing a reliable and ethical alternative to animal models. Its ability to mimic the lung’s environment and respond to pharmacological treatments underscores its potential in advancing our knowledge of lung function, disease mechanisms, and the development of more effective treatments.

1 Alveolar cells are cells that line the alveoli, which are tiny air sacs in the lungs where gas exchange occurs.

2 ARTORG – The Center for Biomedical Engineering Research is a research centre in Bern, Switzerland, renowned for its innovations in healthcare technology.

3 A lung-on-chip model is a bioengineering technology that uses cell biology and microfluidic engineering to create a small environment where living lung cells can survive and imitate lung functions outside of the body.

Authors: Christopher Cederroth, Jessica Lampe & Robbie I’Anson Price, Swiss 3R Competence Centre 

Reference: Sengupta A, Roldan N, Kiener M, Froment L, Raggi G, Imler T, de Maddalena L, Rapet A, May T, Carius P, Schneider-Daum N, Lehr C-M, Kruithof-de Julio M, Geiser T, Marti TM, Stucki JD, Hobi N, and Guenat OT (2022). A New Immortalized Human Alveolar Epithelial Cell Model to Study Lung Injury and Toxicity on a Breathing Lung-On-Chip System. Front. Toxicol. 4:840606. https://doi.org/10.3389/ftox.2022.840606

Georg Därendinger

Georg Därendinger

Member of the Executive Board / Head of Communication

+41 79 590 98 77

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