Researchers at the Wyss Institute in Harvard have developed a microfluidic chip that mimics the airways of patients with cystic fibrosis. By adding lung airway cells from cystic fibrosis patients to the device, the team was able to reproduce many of the hallmarks of the disease, including a thick layer of mucus, inflammation and bacterial growth. The chip could provide the first advanced preclinical test platform for the treatment of cystic fibrosis and improve our understanding of the disease.
This picture shows how neutrophils (fluorescent green) that were added to the blood channel have attached to the endothelium (cells outlined in magenta) and migrate in the parallel channel to the epithelium.
Cystic fibrosis is a hereditary disease and involves the production of thick mucus in the airways and other organs in the body. The progressive condition leads to repeated episodes of infection and inflammation, which eventually lead to lung scars and respiratory failure. While the prognosis for most cystic fibrosis patients has improved significantly over the past few decades, many do not live to be older than 30 or 40, underscoring the urgent need for more effective treatments.
Part of the problem is the lack of reliable in vitro models of cystic fibrosis, making it difficult to test new therapies and understand the dynamics of the disease and the cycle of repeated bacterial infections at the cellular level. These researchers have taken steps to address this, using airway cells from cystic fibrosis patients to create a microfluidic tabletop model that appears very similar to the airway in cystic fibrosis.
The cystic fibrosis chips appear to mimic some of the characteristics of the disease. For example, after several weeks of culture, CF chips contained more inflammatory cytokines, a thicker layer of mucus, and higher concentrations of an introduced bacterium, Pseudomonas aeruginosa, which is involved in cystic fibrosis breast infections. This was in stark contrast to chips that contained airway cells from healthy volunteers.
The cystic fibrosis-mimicking airway tissue on a chip with its secreted mucus layer supported the colonization and growth of the bacterial pathogen Pseudomonas aeruginosa (shown here by green fluorescence), Pseudomonas aeruginosa, which is present in the microbiome of the normal lung, but grows uncontrollably and lung infections in human Cause CF patients.
“This first microphysiological model of a CF airway corresponds exactly to what we know about the airways in CF patients. While maintaining the typical composition of all relevant cell types, it developed a thicker layer of mucus and its ciliated cells have a higher density of fibrillation, which beats at a higher frequency compared to airway chips made with airway cells from healthy people, ”said Ratnakar Potla , one of the developers of the device in an announcement from the Wyss Institute. “It is important that these pathological changes were accompanied by an increased inflammatory reaction in the modeled CF bronchial epithelium, which is very similar to that observed in CF patients.”
“Now that we are able to accurately model CF pathology, including the microbiome and inflammatory responses, in human airway chips, we have a way to address challenges that are important to CF patients,” said Donald Ingber, another researchers involved in the study. “The combined capabilities of this advanced in vitro model can help accelerate the search for drugs that suppress exaggerated immune responses in patients, treat them with more personalized therapies, and help solve problems that CF patients face on a daily basis and which cannot be addressed with existing means. “Treatments.”
Study in the Journal of Cystic Fibrosis: Modeling Pulmonary Cystic Fibrosis in a Human Pulmonary Airway-on-a-Chip
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Via: Harvard Wyss Institute