Although CFTR modulators have improved the lives of people with cystic fibrosis (CF), little is known about their impact on inflammation, which remains a vexing problem in CF. A main problem in CF research is the lack of reliable preclinical models, especially suitable for inflammation studies. In recent years, an innovative technology denominated “organ-on-a-chip” has been developed to deal with this problem using human cells. This technology, faithful reproducing the functional units of human organs, has been exploited in many biomedical research fields, including CF.
In a previous study, the researchers modeled the human CF airways using respiratory cells obtained from people with CF put in contact with human lung endothelial cells to recapitulate the structure of the airways. In this project, they aim to further implement the previous model and make it ready to be used for inflammation and infection studies in CF.
In the updated model, called CF airway-on-a-chip 2.0, the impact of CFTR modulators on the inflammatory response will be tested, in the presence or absence of bacterial infection, as well as the behavior of immune cells in the CF pulmonary disease.ù
The construction of a human preclinical model will be helpful to circumvent many of the problems related to the use of animals for preclinical testing and it will likely improve the prediction of drug efficacy, accelerating the process to develop new and better drugs for the benefit of people with CF.
Since with this technology it is possible to reconstitute other organs, CF airway-on-a-chip 2.0 could be used to generate models of CF intestine, liver or pancreas, in order to study the disease in its complexity and predict pharmacological responses of the patients with the greatest accuracy.