The evidence was particularly striking when the researchers experimented with the composition of the organoids. When these specific HBCs were selectively removed or depleted from the cultures, the entire regenerative process faltered. The generation of new neurons was significantly impaired, proving that the HBCs were not merely waiting in the wings for an emergency, but were active participants in the ongoing health and renewal of the olfactory tissue.
This interdependency between HBCs and GBCs suggests that the health of the "dormant" cell population is just as vital as the health of the "active" population. If the HBCs are compromised, the GBCs cannot effectively carry out the work of creating new sensory neurons. This finding provides a new framework for understanding why the sense of smell might fail to return after certain types of damage; it may not be that the neurons are gone, but that the support system required to rebuild them has been disrupted.
The study also addressed the inevitable decline of sensory function associated with the passage of time. By growing organoids using cells harvested from mice of varying ages, the team was able to observe the aging process in real-time. They found a clear and measurable decline in the ability of cells from older mice to generate new neurons.
"We found a decline in the ability of the older mice cells to generate new neurons," Lin notes. "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."
An Easy-To-Use Model
One of the most significant contributions of this study is not just the biological discovery itself, but the tool used to achieve it. The lead author of the study, Juliana Gutschow Gameiro, a former Ph.D. student who visited the Graduate School of Biomedical Sciences at Tufts from the State University of Londrina in Brazil, was instrumental in designing the organoid model.
From the outset, Gameiro and Lin were committed to creating a model that was accessible. In the world of high-tech biomedical research, many advanced models require exorbitant funding, specialized equipment, and highly specific expertise that many labs around the world simply do not possess. Gameiro’s goal was to democratize the study of olfactory regeneration by developing a 3D model that was easy to create even in resource-limited settings.
The timing of this development is critical. While olfactory research was once a relatively niche field, the global COVID-19 pandemic changed the landscape overnight. Sudden and often prolonged loss of smell became a hallmark symptom of the virus, drawing thousands of researchers from various disciplines into the study of the nasal epithelium. Furthermore, loss of smell is increasingly recognized as an early warning sign for neurodegenerative conditions such as Parkinson’s disease and Alzheimer’s disease.
"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.
