By observing the cells within the organoid model, the team identified a specific subpopulation of HBCs. These particular cells are distinguished by their production of a protein known as KRT5 (Keratin 5). The study found that these KRT5-producing HBCs are not merely sitting in reserve; they are active participants that support the generation of new olfactory neurons.
The evidence for this role was clear: when the researchers selectively removed these specific HBCs from the organoid cultures, the production of new neurons was significantly impaired. This suggests that HBCs provide a necessary "niche" or support system that allows the GBCs to function correctly. Without the influence of the HBCs, the regenerative cycle essentially stalls.
Aging and the Decline of Sensory Regeneration
The study also shed light on one of the most common causes of smell loss: the natural process of aging. It is a well-documented medical fact that the sense of smell often dulls as people enter their later decades, but the cellular mechanism behind this decline has remained somewhat elusive.
To investigate this, the Tufts team utilized their model to compare cells harvested from mice of various ages. The results showed a marked difference in regenerative capacity. Cells taken from older mice were significantly less effective at generating new neurons within the 3D organoid environment.
"We found a decline in the ability of the older mice cells to generate new neurons," Lin noted. "We think this is due to a decrease in the GBC population as we age, but we need to do more work to test this hypothesis and if so, develop ways to rejuvenate them."
This finding is particularly relevant for the development of geriatric medicine. If the decline in smell is tied specifically to the depletion of globose basal cells or the failure of the horizontal basal cells to support them, it opens the door for targeted therapies that could potentially "restart" the regenerative process in older adults.
An Easy-To-Use Model
One of the most significant contributions of this research is the nature of the model itself. In the world of high-level molecular biology, research can often be prohibitively expensive, requiring specialized equipment and massive budgets. However, the lead author of the study, Juliana Gutschow Gameiro, was determined to create a tool that was accessible to the wider scientific community.
Gameiro, a former Ph.D. student who visited the Graduate School of Biomedical Sciences at Tufts from the State University of Londrina in Brazil, focused on developing a 3D olfactory tissue model—or organoid—that was "easy-to-create."
