In the nose, cells do not exist in isolation; they are stacked and interwoven, communicating through physical contact and chemical signals. The Tufts team’s 3D model allows researchers to observe these interactions in real-time. This model is particularly effective at showing how HBCs and GBCs communicate and support one another to develop new smell-sensing nerve tissue.
"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," says Lin.
The accessibility of the model was a primary goal for the study’s lead author, Juliana Gutschow Gameiro. A former Ph.D. student visiting GSBS from the State University of Londrina in Brazil, Gameiro was dedicated to ensuring the model could be replicated in laboratories that might lack the massive funding or high-end equipment of elite research institutions. This "democratization" of the research tool is particularly timely, as interest in the olfactory system has surged in the wake of the pandemic.
"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," Lin notes. By providing a low-cost, high-fidelity model, the Tufts team is opening the door for scientists worldwide to investigate why the sense of smell diminishes or fails completely in various patient populations.
Investigating the Impact of Aging
One of the most pressing questions in olfactory research is why our sense of smell tends to decline as we age. It is a common clinical observation that older adults often lose the ability to detect subtle scents, which can impact everything from their appetite and nutrition to their ability to detect environmental hazards like gas leaks or spoiled food.
Using their new model, the Tufts researchers compared cells harvested from young mice with those from older mice. They found a definitive decline in the ability of the older cells to generate new neurons within the organoid environment.
"We found a decline in the ability of the older mice cells to generate new neurons," Lin says. "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 discovery that the GBC population might be dwindling with age provides a specific target for future therapies. If scientists can find a way to "reboot" these stem cells or supplement the aging tissue with the supportive signals provided by the HBCs, it might be possible to restore a youthful level of regenerative capacity to the aging nose.
