Image by Aron Jaffe of Novartis, first published in Cell Reports
Not to put too fine a point on this, asthma and cystic fibrosis are diseases of mucus—too much mucus, which fills small airways in the lungs and makes it hard to breathe. The flood of mucus comes from bad life choices by basal cells, parent cells that can produce either “goblet” cells (the mucus makers) or ciliated cells (whose tiny hair-like protrusions wave the mucus along the airways). In these diseases, too many goblet cells and too few ciliated cells are produced. So what can persuade the basal cells to make more balanced decisions?
Aron Jaffe of Developmental & Molecular Pathways at the Novartis Institutes for BioMedical Research (NIBR) in Cambridge and his colleagues began to address this question by culturing human basal cells in three dimensions to create “bronchosphere” tissue models.
“This is the first human cell culture that has all three cells: the progenitor basal cells, ciliated cells and goblet cells,” Jaffe says. “We also scaled the system up to 384-well plates, which is probably the big technical hurdle for doing unbiased drug screening.”
In early work with their bronchosphere models, Jaffe and coworkers discovered that inhibiting a protein called Notch2 shifts the balance of cell production back toward ciliated cells, raising the potential of novel treatments for asthma and cystic fibrosis.
Here, in this image of a slice through a healthy bronchosphere taken by confocal microscopy, DNA is shown in blue. Markers for basal cells appear in red, for goblet cells in green, and for ciliated cells in orange.
Learn more about the bronchosphere model in “Asthma researchers muck out mucus cells.”