Research from the Francis Crick Institute and AlveoliX has led to a breakthrough in personalized medicine with the development of a novel lung-on-a-chip model. This model, detailed in a study published on October 25, 2023, in the journal Science Advances, utilizes stem cells from a single human donor to replicate the function of human alveoli, the air sacs in the lungs critical for gas exchange and defense against respiratory diseases.
The innovative lung-on-a-chip technology addresses significant gaps in the study of human respiratory diseases, particularly in creating systems that accurately mimic human immune responses. Traditional models often rely on a mix of patient-derived and commercially available cells, which fail to represent the unique cellular environment of an individual. According to Max Gutierrez, PhD, principal group leader at the Crick, “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.”
A New Approach to Understanding Tuberculosis
The researchers successfully produced type I and II alveolar epithelial cells, as well as vascular endothelial cells, from human-induced pluripotent stem cells (iPSCs). These cells were cultivated on a specialized membrane within a device designed by AlveoliX, which imposed rhythmic three-dimensional stretching forces to simulate breathing motions. This setup allows for a more accurate study of diseases like tuberculosis (TB), which has long posed challenges for researchers due to its slow progression.
In their experiments, the team observed significant pathological changes when the lung-on-a-chip model was infected with Mycobacterium tuberculosis. Five days post-infection, the endothelial and epithelial barriers collapsed, indicating a breakdown in the air sac function. This finding is critical, as it highlights the model’s ability to mimic early disease events, which is essential for understanding how TB develops and progresses.
Jakson Luk, PhD, a postdoctoral fellow at the Crick and the study’s first author, emphasized the importance of studying the initial 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,” Luk noted.
Implications for Future Research and Treatment
The potential applications of this lung-on-a-chip model extend beyond tuberculosis. Researchers are optimistic that it can also be used for investigating other respiratory infections and conditions such as lung cancer. Gutierrez mentioned the prospect of refining the chip by incorporating additional cell types, which could further enhance its relevance for personalized medicine.
This pioneering work marks a significant step forward in the field of respiratory disease research, providing a platform that can facilitate the testing of new treatments tailored to individual patients. By utilizing genetically identical cells derived from a single donor, the model offers a precise tool for understanding how specific genetic mutations may influence an individual’s response to infections like TB and the effectiveness of various antibiotics.
The development of this lung-on-a-chip technology underscores the urgent need for alternatives to animal testing and the importance of creating in vitro models that reflect human biology more accurately. As researchers continue to refine and expand this technology, the promise of personalized medicine becomes increasingly tangible, potentially transforming the landscape of treatment for respiratory diseases.
