Source : WAM
Researchers at the Francis Crick Institute and biotechnology company AlveoliX have created the first human “lung-on-chip” model using genetically identical cells derived from stem cells from a single donor.
The device, designed to replicate breathing movements and the early stages of lung disease, could help scientists test treatments for infections such as tuberculosis (TB) and advance personalized medicine.
Lung air sacs, called alveoli, are critical for gas exchange and also serve as a key barrier against inhaled viruses and bacteria that cause respiratory diseases such as flu or TB.
Scientists have long sought to replicate these processes using “organ-on-chip” technology small units of human tissue grown on plastic chips containing microscopic channels and compartments. Until now, lung-on-chip systems have relied on a mix of patient-derived and commercially available cells, limiting their ability to fully reproduce lung function and disease progression for a single individual.
In a study published in Science Advances, the Crick team developed a new lung-on-chip model using only genetically identical cells derived from stem cells of one donor.
They generated type I and II alveolar epithelial cells and vascular endothelial cells from human-induced pluripotent stem cells, which can become nearly any cell type in the body. The epithelial and endothelial cells were cultured on opposite sides of a thin membrane in a device manufactured by AlveoliX, recreating the barrier of an air sac.
To simulate breathing, AlveoliX designed specialized machines that apply rhythmic, three-dimensional stretching forces to the recreated air sac barrier. This mechanical motion encourages the formation of microvilli, which increase the surface area of alveolar epithelial cells and enhance lung function.
The researchers then introduced immune cells called macrophages, also derived from the same donor’s stem cells, before infecting the chip with TB bacteria to mimic the early stages of the disease.
In the infected chips, macrophages formed large clusters with “necrotic cores,” areas of dead macrophages surrounded by live ones. Five days after infection, the endothelial and epithelial cell barriers collapsed, showing that the air sac function had broken down.
Max Gutierrez, Principal Group Leader of the Host-Pathogen Interactions in Tuberculosis Laboratory at the Crick and senior author, 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.”
