Researchers at the Francis Crick Institute and AlveoliX have developed the first human lung-on-chip model using stem cells taken from only one person.
In a study published in Science Advances, the research team focused on creating a model of air sacs in the lungs to understand how the organ responds to infection, like tuberculosis (TB).
Based on a protocol developed previously by the lab, the team produced type I and II alveolar epithelial cells and vascular endothelial cells from human-induced pluripotent stem cells. These epithelial and endothelial cells are separately grown on the top and bottom of a very thin membrane in a device manufactured by biotechnology company AlveoliX to recreate an air sac barrier.
To simulate the human lung, AlveoliX designed specialized machines to impose rhythmic 3D stretching forces on the recreated air sac barrier, mimicking the motion of breathing. This stimulates the formation of microvilli, a key feature of alveolar epithelial cells to increase surface area for lung functions.
Next, the scientists added immune cells called macrophages into the chip, again produced from the stem cells of the same donor, before adding TB bacteria to simulate the early stages of the disease.
In the chips infected with TB, the team reported large macrophage clusters containing necrotic cores, a group of dead macrophages in the center surrounded by live macrophages. Eventually, five days after infection, the endothelial and epithelial cell barriers collapsed, showing that the air sac function had broken down.
“We were successfully able to mimic these initial events in TB progression, giving a holistic picture of how different lung cells respond to infections,” said first author Jakson Luk, postdoctoral fellow in the Host-Pathogen Interactions in Tuberculosis Laboratory at Francis Crick. “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 important cell types.”
Data from Francis Crick Institute