To test the necessity of these cells, the team conducted an experiment where the KRT5-producing HBCs were selectively depleted from the organoid cultures. The results were stark: without the support of these "dormant" cells, the generation of new olfactory neurons was significantly impaired. This suggests that HBCs are not merely a backup system for emergencies, but are essential players in the day-to-day maintenance of the olfactory system.
Aging and the Decline of Sensory Function
One of the most pressing questions in olfactory science is why our sense of smell tends to fade as we grow older. To investigate this, the research team expanded their study to include cells harvested from mice of various ages.
When these cells were grown within the 3D model, a clear pattern emerged. The cells taken from older mice showed a marked decline in their ability to generate new sensory neurons compared to those from younger mice. The researchers hypothesize that this decline is linked to a diminishing population of globose basal cells (GBCs) as the organism ages.
"We found a decline in the ability of the older mice cells to generate new neurons," Lin explains. "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 provides a potential target for future therapeutic interventions. If scientists can identify the exact mechanisms that cause GBC populations to dwindle, they may be able to develop treatments that "reboot" the regenerative process in older adults, potentially restoring a sense of smell that was previously thought to be lost to time.
An Easy-To-Use Model
The development of the 3D organoid was driven not only by scientific curiosity but also by a commitment to making high-level research accessible to a broader range of scientists. The lead author of the study, Juliana Gutschow Gameiro, played a central role in this effort. A former Ph.D. student visiting the Graduate School of Biomedical Sciences at Tufts from the State University of Londrina in Brazil, Gameiro was dedicated to ensuring the model could be replicated in diverse laboratory settings.
According to Lin, Gameiro’s goal was to create a system that was easy to assemble, even for laboratories with limited budgets or specialized equipment. This "democratization" of the technology is particularly timely given the recent surge in interest in olfactory research.
"Because loss of smell is associated with COVID-19, as well as with Parkinson’s disease and other conditions, a much larger number of researchers from a variety of different fields have begun researching olfactory epithelial cells in the last few years," says Lin.
By providing an easy-to-use model, the Tufts team hopes to lower the barrier to entry for non-stem cell biologists. This allows neurologists, virologists, and toxicologists to incorporate olfactory regeneration studies into their own work, accelerating the pace of discovery across multiple disciplines.
