Researchers conducting a new study have identified the process of how stem cells located in the airways of the lungs switch between two distinct phases. They create more of themselves and produce mature airway cells to regenerate lung tissue following an injury.
The study additionally sheds light on how aging can lead to lung regeneration going awry which can lead to cancer of the lungs and other diseases. Currently there are few therapies that target the biology of diseases that affect the lungs. The new findings will assist researchers in efforts to develop targeted therapies to improve the health of the airway.
The airways carry the air that is breathed in from the mouth and nose to the lungs. They are the body’s first line of defense against airborne particles such as pollution and germs that can lead to illness. The two types of airway stem cells have a vital role in this process. Mucus cells secrete mucus to trap harmful particles. Ciliated cells use their finger like projections to sweep the mucus engulfed particles up to the back of the throat and then cleared out of the lungs.
Infectious and toxic particles which people breathe in every day can lead to injury of the airways. When this happens, airway basal stem cells which are capable of self-renewing and producing mucus and the ciliated cells which line the airways, are activated to repair any damage.
In order to keep the correct balance of each type of cell, airway basal stem cells must transition from the proliferative phase where they produce more of themselves, to the differentiation phase where they give rise to mature airway stem cells.
These particular stem cells must maintain a very delicate equilibrium. They need to produce just the correct amount of mucus and ciliated cells in order to keep harmful particles out of the lungs. They must also self-replicate to ensure there will be enough of these stem cells to respond to the next injury.
For the study, the research team examined mice who had lung injuries. They analyzed how the different kinds of cells found in the supportive environment that surrounds airway basal stem cells, work together to insure the repair response.
They discovered that a group of molecules known as the Wnt/beta-catenin signaling pathway activate to stimulate the basal stem cells found in the airway to respond to injury. They were surprised to discover that this molecule group originates in one cell type to initiate proliferation and a different cell type to initiate differentiation.
During the proliferation phase of repair, a connective tissue cell known as a fibroblast secretes the Wnt molecule which then signals to the stem cell that it is time to self-renew. During the differentiation phase of repair, the Wnt molecule is secreted by an epithelial cell which make up the lining of organs and tissues, to signal to the stem cells that it is time to produce mature airway cells.
Understanding how the regeneration process works in healthy lungs is an important first step to understanding how disease can occur when the process goes wrong. In order to gain insights into what role this process and the cells that activate it could play in disease, the team studied its activity in older mice.
They were surprised to find that in the airways of the aging mice, the Wnt/beta-catenin signaling pathway is active in the stem cells even when there is no injury. This is in contrast to the airways of young mice where it is only activated when necessary. When the pathway is active, it stimulates the stem cells to produce more stem cells and more airway stem cells even when they are not needed.
Early research has established a connection between a more active Wnt/beta-catenin pathway and lung cancer. The more a cell divides, the greater the chance that a mutation or a proofreading error can occur which can lead to cancer.
The new study builds on this work by establishing not only what goes wrong, but exactly when it goes wrong in otherwise healthy people as part of the process of aging. The findings have given researchers insight into which types of stem cells are important, which pathway is also important and when therapies to prevent the formation of cancer might be developed.
To view the original scientific study click below:
Distinct Spatiotemporally Dynamic Wnt-Secreting Niches Regulate Proximal Airway Regeneration and Aging.