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Here’s what you’ll learn when you read this story:
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A new study developed a lung-on-a-chip that was grows from genetically identical cells using a single human stem cell.
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While this provides a platform for understanding how TB overcomes the lung’s defenses, similar chips could help science move away from animal testing and introduce a new era of personalized medicine.
In the U.S., tuberculosis isn’t a medical crisis that is front of mind (though numbers of infections in the country are rising). But in other parts of the world, TB remains an unmitigated disaster. According to the World Health Organization, 10.7 million people were infected with the bacterium Mycobacterium tuberculosis in 2024, and 1.23 million died from the disease. Medical experts see TB’s persistence in poorer countries as a stinging indictment of social inequality—the disease essentially divides human populations into the “haves” and the “have-nots.”
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As such, some scientists are using their time and attention trying to understand how TB overcomes our primary defenses that protect the air sacs in our lungs. Inspired by ever-improving “organ-on-a-chip” technology—which, as its name suggests, aims to create living, functioning models of organs that combine cell cultures with integrated circuits—a team of researchers (led by scientists at the Francis Crick Institute in the U.K.) developed a “lung-on-a-chip” to help them understand what is happening in the time between initial TB infection and the appearance of symptoms. This “black box” period, as the researchers call it, can sometimes last up to months, so understanding how TB reacts during this crucial time is key. The results of the study were published in the journal Science Advances.
“The air sacs in the lungs are a critical first barrier against infections in humans, but we’ve traditionally looked at them in animals like mice,” Max Gutierrez, the senior author of the study and lead of the Host-Pathogen Interactions in Tuberculosis Laboratory, said in a press statement. “These studies are fundamental for our understanding, but animals and humans have differences in the makeup of immune cells and disease progression, sparking interest in alternative technologies.”
What Gutierrez and his team found was that, after introducing immune cells to the lung-on-a-chip before TB infection, these cells (or macrophages) formed “necrotic cores”—essentially clusters of dead cells surrounded by living macrophages. After five days, endothelial and epithelial cell barriers had already collapsed.
Because this new lung-on-a-chip consists of identical cells developed from a single human stem cell, the platform can now provide ways for scientists to test different genetic reactions to TB’s spread.
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“We could now build chips from people with particular genetic mutations to understand how infections like TB will impact them and test the effectiveness of treatments like antibiotics,” Jakson Luk, the lead author of the study from Francis Crick Institute, said in a press statement. “We removed the ATG14 gene, which is involved in a natural process for degrading damaged cells and foreign materials. Macrophages lacking this gene were more susceptible to cell death in resting conditions, and tried to engulf more TB bacteria when infected, confirming the gene’s role in keeping our immune defenses intact.”
Tuberculosis is just one (albeit important) respiratory disease. This new lung-on-a-chip, however, could serve as a vital platform for scientists to study a whole plethora of diseases, all while moving away from animal testing and into a new era of personalized medicine in which a person’s specific genetics can inform treatment.
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