Researchers from the Francis Crick Institute and AlveoliX have developed a groundbreaking lung-on-a-chip model, marking a significant advancement in personalized medicine. This model, outlined in a study published in Science Advances, utilizes stem cells derived from a single human donor to simulate lung function and disease, particularly focusing on infections like Mycobacterium tuberculosis (TB).
The lung-on-a-chip system replicates the breathing motions of human lungs, creating a unique platform for studying respiratory diseases. Traditional models have struggled to accurately reflect the complex interactions within human lungs, often relying on a mix of patient-derived and commercially available cells. The new approach overcomes these limitations by using genetically identical cells, allowing for more precise investigations into how specific genetic variations may influence disease progression and treatment efficacy.
A Revolutionary Approach to Lung Research
The development of this model addresses a critical gap in the study of human respiratory diseases. Max Gutierrez, PhD, principal group leader at the Crick and corresponding author of the study, noted, “Given the increasing need for non-animal technologies, organ-on-chip approaches are becoming ever more important to recreate human systems.” The chips can be customized to reflect the genetic makeup of individuals, which is particularly valuable for understanding diseases like TB that exhibit variability in symptoms and responses to treatment.
To create the lung model, researchers produced type I and II alveolar epithelial cells alongside vascular endothelial cells from human-induced pluripotent stem cells (iPSCs). These cells were cultivated on a specialized membrane, allowing them to form a barrier similar to the air sacs in human lungs. The incorporation of technology from AlveoliX enabled the researchers to impose rhythmic three-dimensional stretching forces, mimicking the natural motions of breathing.
In experimental settings, the researchers observed that when the lung-on-a-chip model was infected with TB, it developed large clusters of macrophages—immune cells involved in fighting infections. After five days, the barriers formed by endothelial and epithelial cells began to collapse, indicating a breakdown in lung function. This finding is crucial, as TB is a slow-progressing disease, often taking months for symptoms to appear.
Implications for Future Research
Dr. Jakson Luk, a postdoctoral fellow at the Crick and the study’s first author, emphasized the importance of understanding the early stages of TB progression. “We were successfully able to mimic these initial events in TB progression, giving a holistic picture of how different lung cells respond to infections,” he explained. The model holds promise not only for TB research but also for exploring other respiratory infections and conditions such as lung cancer.
The research team plans to refine the lung-on-a-chip model further by integrating additional cell types, which could enhance its effectiveness as a research tool. The potential applications of this technology are vast, offering new avenues for personalized treatment strategies that consider individual genetic variations.
The advancement of the lung-on-a-chip model represents a significant step forward in the field of biomedical research, promising to enhance our understanding of complex respiratory diseases and leading to more effective, tailored therapies.
