"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," said Lin.
The surge in interest following the pandemic meant that scientists who were not necessarily experts in stem cell biology were suddenly tasked with understanding the nasal environment. By making the model simple and inexpensive, the Tufts team has provided a platform for labs with limited resources to conduct high-quality research. This democratization of the technology allows for a more diverse range of studies into how neurons are formed and what causes the process to fail in the face of disease.
Next Step: A Human Organoid
While the current success involves a mouse-tissue model, the researchers have their sights set on a much larger goal: the creation of a human olfactory organoid. Such a model would represent a massive leap forward for clinical medicine, acting as a bridge between laboratory research and patient care.
In the modern drug development pipeline, organoids are becoming increasingly vital. They allow for pre-clinical trials that are faster, cheaper, and often more accurate than animal testing. Because an organoid is grown from actual tissue, it can provide a realistic preview of how a human organ might respond to a specific drug or treatment. While organoids have already been successfully developed for the lungs, kidneys, and liver, the human olfactory system has proven to be a much tougher nut to crack.
The primary obstacle is the difficulty of obtaining pure, uncontaminated human olfactory tissue. Unlike mice, where tissue can be harvested with precision, collecting samples from humans is an invasive and complicated process. It typically involves anesthetizing the patient and using a specialized brush—similar to the swabs used for COVID-19 tests but pushed much deeper into the nasal cavity—to scrape the upper reaches of the nose.
The challenge, according to Lin, is that this process inevitably collects a mixture of different cell types. "It’s challenging to get pure olfactory tissue from humans," he explained. In the resulting sample, human respiratory stem cells are often mixed with olfactory stem cells, and currently, they are extremely difficult to separate.
The research team’s next major hurdle is to refine their techniques to isolate these human olfactory stem cells. Once they can separate these cells from the surrounding respiratory tissue, they can begin coaxing them to grow into 3D organoids in the lab.
The ultimate vision is a future where a patient suffering from chronic smell loss—whether from long-COVID, neurodegenerative disease, or age—could have their own cells used to grow a personalized organoid. Doctors could then use that organoid to screen various drugs and regenerative therapies to see which one works best for that specific individual before ever starting a clinical trial.
By uncovering the "hidden" power of horizontal basal cells and providing a blueprint for accessible 3D modeling, the Tufts researchers have not only deepened our understanding of the nose but have also provided a new sense of hope for restoring one of our most vital connections to the world around us.
