Researchers at Harvard’s Wyss Institute created a microfluidic chip that mimics the airway of patients with cystic fibrosis. By including lung airway cells from cystic fibrosis patients within the device, the team was able to reproduce many of the hallmarks of the disease, including a thick mucus layer, inflammation, and bacterial growth. The chip could provide the first advanced preclinical testing platform for cystic fibrosis treatments and increase our understanding of the disease.
This image shows how neutrophils (fluorescing in green) that were added to the blood channel have attached themselves to the endothelium (with cells outlined with a marker shown in magenta) and transmigrate to the epithelium in the parallel channel.
Cystic fibrosis is an inherited disease and involves the production of thick mucus within the airways and in other organs in the body. The progressive condition results in repeated episodes of infection and inflammation, which eventually cause lung scarring and respiratory failure. While the prognosis for most cystic fibrosis patients has improved considerably in recent decades, many do not live beyond their 30s or 40s, highlighting the dire need for more effective treatments.
Part of the problem involves a lack of reliable in vitro models of cystic fibrosis that makes it difficult to test new therapies, and understand the dynamics of the disease and the cycle of repeated bacterial infection on a cellular level. These researchers have taken steps to address this, and have used airway cells from cystic fibrosis patients to create a benchtop microfluidic model that appears to closely resemble the airway in cystic fibrosis.
The cystic fibrosis chips appear to mimic some of the characteristics of the disease. For instance, after a culture period of several weeks, CF chips contained more inflammatory cytokines, a thicker mucus layer, and higher levels of an introduced bacterium, Pseudomonas aeruginosa, which is implicated in cystic fibrosis chest infections. This was in stark contrast with 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 normal lung but can grow out of control and cause lung infections in human CF patients.
“This first microphysiological model of a CF airway closely mimics what we know from airways in CF patients. Maintaining the typical composition of all relevant cell types, it developed a thicker mucus layer, and its ciliated cells exhibit higher densities of cilia that beat at a higher frequency compared to Airway Chips created with airway cells from healthy individuals,” said Ratnakar Potla, one of the developers of the device, in a Wyss Institute announcement. “Importantly, these pathological changes were accompanied by an enhanced inflammatory response in the modeled CF bronchial epithelium that is much like the one observed in CF patients.”
“Now that we are able to accurately model CF pathology, including microbiome and inflammatory responses, in human Airway Chips, we have a way to attack challenges that are important to CF patients,” said Donald Ingber, another researcher involved in the study. “The bundled capabilities of this advanced in vitro model can help accelerate the search for drugs that may dampen the exaggerated immune response in patients, treat them with more personalized therapies and, help solve problems that CF patients face every day which cannot be addressed by existing treatments.”
Study in Journal of Cystic Fibrosis: Modeling pulmonary cystic fibrosis in a human lung airway-on-a-chip
Flashbacks: Intestine on a Chip Technique Opens Door to Personalized Medicine; Scientists Develop Bone Marrow-On-A-Chip, Hope to Replace Animals in Pre-Clinical Research; Wyss Institute to Commercialize Its Organs-on-Chips Technology; Scientists Use Organ on Chip to Grow New Kidney Cells; Blood-Vessel-On-a-Chip Helps Identify Safer Clot Prevention Drug
Via: Harvard Wyss Institute