An Easy-To-Use Model for Global Research
The development of the organoid itself represents a significant leap forward in bioengineering, particularly in its accessibility. The lead author of the study, Juliana Gutschow Gameiro, joined the Tufts team as a visiting Ph.D. student from the State University of Londrina in Brazil. Her mission was to create a model that was not only biologically accurate but also practical for labs that may lack the massive budgets or specialized equipment of elite Western institutions.
The resulting mouse-tissue organoid is designed to be "easy-to-create," a feature that Brian Lin emphasizes is critical for the current scientific climate. The global pandemic brought the issue of olfactory dysfunction into the mainstream, as millions of COVID-19 patients reported a sudden loss of taste and smell. This has sparked a surge of interest from researchers who may not be experts in stem cell biology but are eager to find clinical solutions.
"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. "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."
By democratizing access to this type of 3D modeling, the Tufts team hopes to accelerate the pace of discovery across the globe, allowing more scientists to test how different chemicals, viruses, or genetic factors influence the health of nasal neurons.
The Impact of Aging and the Quest for Rejuvenation
One of the most pressing questions in olfactory research is why our sense of smell fades as we grow older. It is a common clinical observation that elderly individuals often lose the ability to detect subtle scents, which can lead to decreased appetite, poor nutrition, and an inability to detect hazards like leaking gas or spoiled food.
The Tufts researchers used their model to investigate this decline by growing organoids from the cells of mice of various ages. Their observations confirmed a clear downward trend: cells harvested from older mice were significantly less capable of generating new neurons than those from younger mice.
"We found a decline in the ability of the older mice cells to generate new neurons," Lin notes. The team believes this failure is tied to a dwindling population of GBCs as the animal ages. However, the discovery of the HBCs’ supportive role adds a new layer to this mystery. If HBCs are required to support GBCs, is the aging of the "dormant" cells the real bottleneck?
"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," Lin says. The organoid model provides the perfect "test kitchen" for these rejuvenation experiments, allowing researchers to introduce different growth factors or drugs to see if the youthful regenerative capacity of the tissue can be restored.
