Скачать или смотреть Restoring airway integrity for people living with cystic fibrosis

University of Geneva researchers reveal a technique to restore airway integrity in cystic fibrosis patients. The researchers found that applying a simple liquid film effectively seals the airway cell lining, lowering the risk of bacterial infection for someone living with cystic fibrosis. This breakthrough suggests mucus hydration as a viable treatment to restore the airways of people living with cystic fibrosis, potentially surpassing existing current therapies which are only prescribed for a specific population of people with the condition.

In the study, published in Cells, the researchers used a model to replicate a respiratory epithelium – which is a protective tissue cell monolayer. Their model demonstrates that hydrating the surface of these areas within the airways of people with cystic fibrosis can restore this protective barrier, countering unwanted bacteria.

Cystic fibrosis, a rare genetic disease caused by CFTR gene mutations, presents severe symptoms including chronic bacterial infections and respiratory failure. The CFTR gene, typically regulating water transport across cell membranes, serves as a gatekeeper for a robust cell barrier defence. Normally, airway epithelial cells create a tight barrier against bacterial colonisation, aided by lubricating mucus that traps microbes. In cystic fibrosis, this barrier weakens, and mucus consistency changes, compromising its gatekeeping role. Altered CFTR protein results in loose cell connections and dehydrated mucus accumulation, contributing to recurrent respiratory infections for those with this condition. The researchers’ aim is to understand these mechanisms, which they hope can lead them to improved treatments for cystic fibrosis.

“While it was already known that mucus hydration and the presence of sufficiently tight junctions preserved the integrity of the airways, the mechanisms involved and the links between these two mechanisms remained mysterious, which hindered the development of new therapies,” explains Marc Chanson, author on the paper.

The researchers had previously developed an in vitro model using human lung cells. This model, which was awarded the UNIGE 3R Prize in 2021 for reducing animal experimentation, reproduced accurate airways epithelium of healthy and cystic fibrosis patients.

In the current study, the model was used to compare how epithelial cells responded to bacterial infection when exposed to either hydrated mucus, healthy mucus, or saline solution. Their results suggest that an epithelial integrity gatekeeper is influenced by the presence of an apical liquid, regardless of its composition or the presence of functional CFTR expression.

Author on the paper Juliette Simonin, explains that surface hydration sufficiently tightens cell junctions and safeguards the epithelium integrity from bacterial colonisation, even when CFTR is not functioning.
“We observed a similar response in both cases: the presence of liquid, whatever its composition, restored the airways and protected them from infection,” says Simonin.

While a triple therapy targeting the CFTR protein is currently available, it is limited to certain CFTR gene mutations and a specific group of cystic fibrosis patients. This highlights the urgent need for broader, safer treatment options that can benefit all cystic fibrosis patients.
This discovery's success opens doors for mucus hydration-based therapies as a promising alternative to current, often less effective treatments.

“Our results provide evidence that rehydration of the airway surface is beneficial. The challenge now is to find a simple way of doing this in all people with the disease, whatever the mutation involved,” says Chanson.
If you're interested in learning more about this research, you can access the paper published in the Cells here: https://shorturl.at/gkoBR