Stem cells offer protective effects for damaged lung cells exposed to cigarette smoking by alleviating oxidative stress in mitochondria, a study shows. These results were also observed in mice and suggest a potential new therapeutic strategy for oxidative stress-dependent lung diseases, such as chronic obstructive pulmonary disease (COPD).
The study “Mesenchymal stem cells alleviate oxidative stress-induced mitochondrial dysfunction in the airways” was published in The Journal of Allergy and Clinical Immunology, and led by researchers at the Imperial College London and Hong Kong University (HKU).
The study examined the effects of cigarette smoke on smooth muscle cells taken from human lungs.
Researchers found that these cells become damaged and are more likely to undergo “suicide,” a cellular process known as programmed cell death or apoptosis.
Cigarette smoke is particularly damaging to mitochondria — small organelles inside cells that are responsible for energy production. In COPD, previous studies showed that mitochondrial dysfunction is one of the factors contributing to inflammation.
When researchers cultured lung cells together with stem cells in the presence of cigarette smoke, lung cells were less prone to undergo apoptosis, suggesting that stem cells may exert a protective effect.
Examining the lung cells’ mitochondria, researchers found that stem cells lessen damage to these structures, namely by decreasing the generation of harmful reactive oxygen species (ROS). ROS are chemically reactive compounds containing oxygen; when in high concentration, ROS can cause damage to cell structures in a process called oxidative stress.
Remarkably, the team found that mitochondria can move from stem cells into neighboring damaged lung cells, restoring their function. This process was enhanced when cells were exposed to cigarette smoke.
In tissue exposed to cigarette smoke – which contains free radicals that can induce oxidative stress – mitochondria became more sluggish and less efficient at producing energy. These damaged cells were also more likely to undergo apoptosis.
Next, researchers investigated these effects in mice.
They first treated the animals with ozone gas to induce oxidative stress and its damaging effects to mitochondria. Mice then received an infusion of stem cells intravenously, i.e., directly into blood circulation.
Researchers observed that stem cell infusion eased ozone-induced mitochondrial dysfunction and inflammation in mouse lungs.
“This study shows that some of detrimental effects of cigarette smoke or ozone can be alleviated in the cells and whole animal, by treatment with stem cells. What our work provides is the potential for cell-based therapies for one aspect of COPD – oxidative stress” Pank Bhavsar, a study senior author, said in a press release.
Cell-based therapies, such as those relying on stem cells, are often difficult to implement due to the high number of cells required.
In this case, however, researchers are optimistic. As Bhavsar noted, “within 24 hours of giving the stem cells to the mice we observed an improvement in lung function, so we know that even though very few cells are getting to lung they are still having an impact.
“In future we might have the ability to re-colonise those areas which have been damaged by disease and reverse the destruction that has occurred. At the moment, the evidence we have is more to do with the interaction between diseased cells and mitochondria, which may have a therapeutic benefit,” Bhavsar concluded.
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