Lung disease: Drugs seem to help regenerate mouse lungs damaged by cigarette smoke

Two drugs that are currently available in clinical trials have been shown to be effective in restoring the regenerative ability of mouse lung cells. This suggests they could be used for chronic obstructive and/or restrictive pulmonary disease.

Two drugs currently in clinical use may help to regenerate the lungs of mice that have been damaged from cigarette smoking. The preliminary results suggest that the drugs could be used to reverse lung damage in patients with chronic obstructive Pulmonary Disease (COPD), which has no cure currently.

COPD is the third leading cause worldwide of death after stroke and heart disease. It can also be caused by smoking. air pollutionOr genetics. It causes an overactive immune response that irreversibly damages lungs, leading in shortness of breath, chest tightness, and high mucus levels.

“The problem with COPD at the moment is that we do not have a way of preventing the progression of disease and the decline in lung function. We have only ways to treat symptoms, such as with anti-inflammatory drugs and inhaled bronchodilators. [which relax lung muscles and widen the airways],” says Reinoud GosensThe University of Groningen (Netherlands).

COPD damages epithelial progenitor cell, which normally regenerate the linings of the lungs. They cannot repair themselves. The only treatment for this has been invasive cellular therapies like stem cell implants, which are a source of progenitor cell.

A drug-based treatment may be more accessible on a larger scale. It can be used alone or in combination. Gosens and his collaborators analysed data from COPD patients and mice that had been exposed to cigarette smoke to identify which genes were more active in diseased lung tissues than healthy controls.

They were able to identify two proteins in epithelial precursor cells that caused the disease. These two proteins could be targeted with two drugs: iloprost which is used for high blood pressure in the lungs, and misoprostol which is used to heal stomach ulcers.

The team exposed mice for four months to cigarette smoke in order to test the drugs. The team then took the mice’s lung progenitor cells and grew them in gel for 14 days in either a drug- or non-drug-containing dishes.

“You take the progenitor cells and place them in a gel, then they form these mini-lung structures known as organoids,” says Gosens.

The team compared the formation of organoids in the presence and absence of the drugs. They found that both drugs seemed to fully restore the progenitor cell’s regenerative capacity, which had decreased after cigarette smoke exposure. The drugs had the same beneficial effect as the previous extracts of lung progenitor cells.

“Compared to other drugs that can support lung regeneration in animals, the big benefit of the drugs we’ve identified is that they’re already used to treat other conditions, so we know that they are safe and they are similarly effective,” says Gosens.

Further analysis revealed that the drugs work by restoring the circadian clocks within the lung cells. These clocks are affected by smoke exposure.

Although organoid formation may indicate the potential for regenerative power of cells, more research is needed to confirm that drugs actually kick-start this process.

“The idea behind this work is wonderful. I’m really delighted to see people working on regenerative power using drugs in COPD. The model is based on mice with a lifespan of 20 years. COPD patients are typically around 50, and we know that regenerative power decreases with age. Better models are needed to really establish therapeutic potential,” says Rolf ZiescheVienna Medical University, Austria

Journal reference: Science Advances, DOI: 10.1126/sciadv.abj9949

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