Breathing New Life into Lung Research: ‘Lung-on-a-Chip’ Mimics Human Disease with Unprecedented Accuracy
A groundbreaking “lung-on-a-chip” model, developed by researchers at the Francis Crick institute and AlveoliX, promises to revolutionize the study of respiratory illnesses and accelerate the development of personalized treatments. This innovative technology utilizes stem cells from a single individual to recreate the complex habitat of the human lung, offering a more accurate and relevant platform for research than previous methods.
The human lung’s air sacs, known as alveoli, are critical for gas exchange but also serve as the primary entry point for inhaled pathogens like viruses and bacteria responsible for illnesses such as influenza and tuberculosis (TB). Scientists have long sought to replicate this intricate interplay between human cells and infectious agents in a laboratory setting. Existing “lung-on-a-chip” devices, however, typically rely on a mixture of cells from various sources, limiting their ability to fully mirror the unique characteristics of an individual’s lung function and disease progression.
This new model overcomes these limitations by utilizing only genetically identical cells derived from human-induced pluripotent stem cells – cells with the remarkable ability to differentiate into virtually any cell type in the body. Researchers successfully generated type I and II alveolar epithelial cells,alongside vascular endothelial cells,from a single donor’s stem cells. These cells were then grown on a specialized chip manufactured by AlveoliX, designed to mimic the structure of an air sac.
To further enhance the realism of the model, AlveoliX incorporated machines that apply rhythmic, three-dimensional stretching forces to the recreated air sac barrier, faithfully replicating the mechanics of breathing. This stimulation encourages the formation of microvilli – tiny projections on the surface of alveolar epithelial cells – which significantly increase the surface area available for crucial lung functions.
The research team then introduced immune cells,specifically macrophages,also derived from the same donor’s stem cells,into the chip. Afterward, they introduced TB bacteria to simulate the early stages of infection. Observations revealed the formation of large clusters of macrophages containing necrotic cores – areas of dead cells surrounded by live macrophages – mirroring the pathology of TB infection. Within five days, the endothelial and epithelial cell barriers collapsed, demonstrating a breakdown in air sac function.
“Given the increasing need for non-animal technologies, organ-on-chip approaches are becoming ever more critically important to recreate human systems,” stated a senior researcher involved in the study. “Avoiding differences in lung anatomy, the makeup of immune cells, and disease development between animals and humans is crucial for reliable research.” The ability to construct these chips from stem cells sourced from individuals with specific genetic mutations opens up exciting possibilities for understanding how infections like TB impact different people and for testing the efficacy of targeted treatments, such as antibiotics.
Another researcher emphasized the importance of studying the early stages of TB, a slow-progressing disease where symptoms can take months to appear. “We were successfully able to mimic these initial events in TB progression, giving a holistic picture of how different lung cells respond to infections,” they explained. “We’re excited that the new model could be applied to a huge range of research,such as other respiratory infections or lung cancer,and we’re now looking at refining the chip by incorporating other critically important cell types.”
The findings, published January 1, 2026, in the journal Science Advances, represent a significant step forward in lung disease research. This innovative “lung-on-a-chip” technology holds immense promise for accelerating the development of more effective and personalized therapies for a wide range of respiratory illnesses.
More information:
Chak Hon Luk et al, Autologous human iPSC-derived Alveolus-on-Chip reveals early pathological events of M. tuberculosis infection,Science Advances (2026).DOI: 10.1126/sciadv.aea9874. www.science.org/doi/10.1126/sciadv.aea9874
Provided by
The Francis Crick Institute
