The research team utilized their 3D model to compare the regenerative capacities of cells harvested from mice of different ages. They found a clear correlation between age and a decline in the ability to produce 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."
The implications of this finding are significant. If the loss of smell in aging is driven by a depletion of the GBC population or a breakdown in the communication between HBCs and GBCs, it may be possible to develop therapeutic interventions. The goal would be to "reboot" these stem cell populations, essentially tricking the nasal tissue into a more youthful state of high-turnover regeneration.
An Easy-To-Use Model
One of the most significant contributions of this research is not just the biological discovery itself, but the tool used to achieve it. The 3D olfactory organoid developed by the team was designed with a specific philosophy in mind: accessibility.
The lead author of the study, Juliana Gutschow Gameiro, was a visiting Ph.D. student at GSBS from the State University of Londrina in Brazil. Her presence at Tufts was driven by a desire to create a research model that did not require the astronomical budgets or high-end specialized equipment often found in elite Western institutions.
"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.
The sudden global focus on anosmia during the pandemic highlighted a gap in the available research tools. While many labs wanted to study the nasal epithelium, many were deterred by the complexity and cost of maintaining primary cell cultures or animal models. By creating an "easy-to-create" 3D organoid, Gameiro and the Tufts team have democratized this area of study.
"We wanted to develop an easy-to-use model so that non-stem cell biologists and those working in labs with limited resources could use it to better understand how olfactory neurons regenerate and what happens that causes that process to diminish or fail completely," Lin explains.
