Beyond the basic mechanics of regeneration, the study also sought to address the common clinical observation that the sense of smell fades with age. The researchers utilized cells harvested from mice of varying ages to grow organoids, comparing the regenerative potential of young tissue against that of older specimens. The results were telling: there was a marked decline in the ability of cells from older mice to produce new sensory neurons.
Lin explains that this decline appears to be linked to changes in the stem cell populations over time. The team believes that as an organism ages, the population of globose basal cells (GBCs) begins to dwindle, or their ability to divide becomes compromised. While the HBCs may still be present, the loss of their cellular partners—the GBCs—disrupts the "interdependent" cycle of growth. Lin emphasizes that more work is required to fully test this hypothesis, but the ultimate goal is to find ways to rejuvenate these aging cell populations, potentially restoring 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. The development of the 3D organoid was led by 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. From the outset, Gameiro and Lin were committed to creating a research tool that was not only effective but also accessible to the wider scientific community.
In the world of high-level biological research, many advanced models require exorbitant funding, specialized equipment, and highly specific expertise in stem cell biology. Gameiro’s model was designed to bypass these barriers. By creating an organoid that is relatively easy to produce and maintain, the team has provided a blueprint that can be used by labs with limited resources.
This accessibility is particularly timely. In the wake of the global pandemic, the study of the olfactory system has moved from a niche interest to a major focus of medical research. The prevalence of "long COVID" symptoms, which frequently include a persistent lack of taste and smell, has drawn researchers from diverse fields—such as neurology, immunology, and gerontology—into the study of olfactory epithelial cells.
Lin highlights the importance of this cross-disciplinary interest, noting that the team wanted to develop a tool that non-stem cell biologists could easily adopt. By lowering the barrier to entry, they hope to accelerate the global understanding of how olfactory neurons regenerate and, conversely, what specific triggers cause that process to diminish or fail entirely in the face of disease.
