UCLA Researchers Show How Respiratory Stem Cells Regenerate

UCLA researchers identified the process by which respiratory stem cells regenerate lung tissue after injury and the abnormalities that can lead to lung cancer.

Lung Cancer

Lung Cancer

As the body’s first line of defense against germs and pollution, the airways consist of two types of cells.  One type secretes mucus to trap harmful particles and the other type made of ciliated cells sweep mucus particles with their cilia into the back of the throat where they can be removed from the lungs.

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The infectious or toxic particles that people breathe in every day can damage their airways. When this happens, the basal stem cells of the airways – which are capable of renewing themselves and producing the mucus and ciliary cells that line the airways – are activated to repair the damage.

An identified cell regeneration process

But how is the balance between these two cells maintained? This is the role of the basal respiratory stem cells, from which each of the mature cells in the respiratory tract develops. “These stem cells must maintain a truly delicate balance,” said Dr. Brigitte Gomperts, Professor and Vice President of Pediatric Hematology-Oncology Research at UCLA Children’s Discovery and Innovation Institute. They must produce just the right amount of mucus and cilia to prevent harmful particles from entering the lungs, but they must also replicate themselves to ensure that there are enough stem cells to respond to the next injury.

In a study published in the journal Cell Stem Cell, researchers from the University of California Los Angeles analyzed the processes of proliferation and differentiation of basal stem cells, which are essential for the regeneration of lung tissue.

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They found that a group of molecules, known as the Wnt/beta-catenin signaling pathway, is activated to stimulate basal respiratory tract stem cells to respond to injury. In the repair proliferation phase, a connective tissue cell called fibroblast secretes the Wnt molecule, which signals the stem cells that it is time for them to renew. In the differentiation repair phase, the Wnt molecule is secreted by an epithelial cell, the lining of tissues and organs, to signal the stem cells that it is time for them to produce mature respiratory cells.

Anomalies that cause disease

By studying the activity of lung stem cells in elderly rats, researchers discovered that a signaling pathway called Wnt/beta-catenin in the stem cells is active even without injury. However, this does not occur in young airways, where the pathway is only activated when needed. “When this pathway is active, it stimulates the stem cells to produce more of themselves and more cells from the airways – even when they are not needed,” notes Cody Aros, the lead author of the paper.

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Earlier work by the same team had already shown that a more active Wnt/beta-catenin signaling pathway could be associated with the development of lung cancer. This new study goes one step further and shows when the aging process can lead to false lung regeneration, which leads to lung cancer and other diseases.

“These results allow us to know which cell types are important, which pathway is important, and when we can consider intervening with therapies to prevent cancer formation,” concludes Cody Aros.

References

Distinct Spatiotemporally Dynamic Wnt-Secreting Niches Regulate Proximal Airway Regeneration and Aging

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