Researchers from the Francis Crick Institute and AlveoliX have created a new human 'lung-on-chip' model using stem cells taken from a single donor. This development marks the first time that such a device has been built exclusively from genetically identical cells derived from one person.
The lung-on-chip simulates both breathing motions and the progression of lung disease in an individual, offering potential for testing treatments for infections such as tuberculosis (TB) and supporting personalized medicine efforts. The device recreates the air sacs, or alveoli, which are critical for gas exchange and serve as barriers against inhaled pathogens responsible for respiratory illnesses like flu and TB.
Traditionally, lung-on-chip devices have combined patient-derived and commercially sourced cells, limiting their ability to accurately replicate the lung function or disease response of a single person. The study, published in Science Advances, details how researchers produced type I and II alveolar epithelial cells along with vascular endothelial cells from human-induced pluripotent stem cells. These were grown on either side of a thin membrane within a device manufactured by AlveoliX to recreate an air sac barrier.
To mimic natural breathing movements, AlveoliX developed specialized machines that apply rhythmic three-dimensional stretching forces to the recreated air sac barrier. This process encourages the formation of microvilli—structures that increase surface area in alveolar epithelial cells, aiding lung function.
The team then introduced immune cells known as macrophages into the chip, also derived from the same donor's stem cells. Tuberculosis bacteria were added to simulate early-stage infection. Infected chips showed clusters of macrophages forming necrotic cores—dead macrophages surrounded by living ones. After five days of infection, both endothelial and epithelial cell barriers failed, indicating loss of air sac function.
Max Gutierrez, Principal Group Leader at the Host-Pathogen Interactions in Tuberculosis Laboratory at the Crick and senior author of the study, said: "Given the increasing need for non-animal technologies, organ-on-chip approaches are becoming ever more important to recreate human systems, avoiding differences in lung anatomy, makeup of immune cells and disease development between animals and humans.
"Composed of entirely genetically identical cells, the chips could be built from stem cells from people with particular genetic mutations. This would allow us to understand how infections like TB will impact an individual and test the effectiveness of treatments like antibiotics."
