Researchers at UCLA have identified a new
stem cell that participates in the repair of the lungs’ large airways, which
play a vital role in protecting the body from infectious agents and toxins in
the environment.
The airways protect the body by generating
and clearing mucus, which is largely produced by the airways’ specialized mucus
glands. While the mechanisms of normal and excessive mucus production are not
well understood, this newly discovered lung stem cell for the mucus glands will
likely yield insights into this critical process.
The study, by scientists at the Eli and
Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA,
represents the first time anyone has found the cell of origin for the many
types of cells that make up the mucus glands and which can also repair the
surface epithelium. The finding, the study states, is of “major importance
to the field of lung regeneration.”
“We’re very excited that we found this
population of cells because it will allow us to study mechanisms of diseases of
the upper airway,” said Dr. Brigitte Gomperts, a UCLA assistant professor
of pediatrics and hematology–oncology and the study’s senior author. “For
example, there currently are no treatments for excess mucus production, which
we see in cystic fibrosis, asthma, and chronic obstructive pulmonary disease.
But if we can understand the mechanisms of how these stem cells repair the
mucus glands, then we may be able to find a way to put the brakes on the system
and prevent mucus over-production.”
The study is published in Stem Cells.
Ahmed Hegab, a UCLA postdoctoral scholar in
Gomperts lab and the first author of the study, named the newly discovered
cells “sub-mucosal gland duct stem cells” because they are found in
the ducts where mucus is first secreted. Hegab and Gomperts had been looking
for the lung stem cells for years and had created a model of repair of the
airways in order to identify the location of the stem cells.
Once Gomperts and her team proved that the
lung stem cells existed and found where they “lived,” they set out to
isolate them and confirm that they could self-renew—that is, grow more of
themselves—and differentiate, turning into the cells that make up the mucus glands
and surface epithelium. The researchers created model systems in which these
isolated stem cells did, in fact, make mucus glands with all the types of cells
required to make mucus and repair the surface barrier of the large airways.
“Our ability to identify the stem cells
and their regenerative ability has implications for the possible identification
of novel therapeutic targets for airway diseases and potential cell-based
therapies in the future,” the study states.
The stem cells also may play a role in tumor
initiation in lung cancer—when the repair goes awry—although further study is
needed to confirm this, said Gomperts, who is also a member of UCLA’s Jonsson Comprehensive Cancer
Center.
