"We also looked at cells from mice of different ages and grew them in the model," Lin explains. "We found a decline in the ability of the older mice cells to generate new neurons. 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."
By identifying exactly which cell populations are dwindling or losing efficacy over time, researchers hope to eventually develop targeted therapies that can "re-prime" the nasal stem cells, effectively turning back the clock on the olfactory system and restoring lost sensory function to the elderly.
An Easy-To-Use Model
One of the most significant contributions of this study is the nature of the model itself. While high-tech laboratory "organs-on-a-chip" and complex organoids are becoming more common, they often require specialized equipment and significant financial investment, which can gatekeep research and slow the pace of discovery.
The lead author of the study, Juliana Gutschow Gameiro, recognized this hurdle early on. A former Ph.D. student visiting the Graduate School of Biomedical Sciences from the State University of Londrina in Paraná, Brazil, Gameiro was dedicated to creating a model that was accessible. Her goal was to design a system that could be replicated in laboratories with limited funds and standard equipment, ensuring that the study of olfactory regeneration is not restricted to only the most well-funded institutions.
According to Lin, this accessibility is more important now than ever. "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," he says.
The sudden global focus on anosmia during the pandemic revealed how little was known about the long-term recovery of nasal tissue. By providing an "easy-to-use" model, the Tufts team is offering a standardized platform for non-stem cell biologists and researchers across disciplines to study how these neurons regenerate and, perhaps more importantly, why that process fails in the face of disease. Whether it is investigating the neurodegenerative pathways of Parkinson’s or the inflammatory response to a viral infection, the organoid provides a clear, three-dimensional view of the cellular interactions at play.
Next Step: A Human Organoid
