"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 noted.
By providing a simplified, reproducible model, the Tufts team hopes to enable researchers who are not necessarily stem cell specialists to study the nasal cavity. Whether a scientist is investigating the impact of a specific virus or testing the toxicity of an industrial chemical, the 3D organoid offers a platform to observe how those factors affect the delicate balance of HBCs and GBCs without the need for complex animal surgeries or prohibitively expensive technology.
Next Step: A Human Organoid
While the mouse-based organoid has already yielded significant insights, the researchers are already looking toward the next major milestone: the creation of a human olfactory organoid. The transition from animal models to human tissue is a critical step in the development of medical treatments, as it allows for more accurate drug screening and a better understanding of human-specific disease pathways.
The use of organoids in pre-clinical research offers several advantages over traditional methods. They are faster and less expensive to maintain than whole animal colonies, and they provide a more realistic three-dimensional environment than flat, two-dimensional cell cultures. Organoids have already been successfully developed for other major organs, including the lungs and kidneys, but the human olfactory system has proven to be a unique challenge.
The primary hurdle lies in the collection of pure tissue. "It’s challenging to get pure olfactory tissue from humans," Lin explained. To collect these cells, patients must be anesthetized while a specialized brush—similar to the swabs used for COVID-19 testing, but designed to reach much deeper into the nasal vault—is used to harvest tissue.
The difficulty arises once the cells are out of the body. In humans, the stem cells for the respiratory system and the stem cells for the olfactory system are physically intermingled. In the current collection process, it is extremely difficult to separate the two. For an organoid to be effective, it must be composed of the correct cell types; a "human olfactory organoid" contaminated with too many respiratory cells would not accurately reflect how the sense of smell functions or fails.
The research team’s next challenge is to develop a simple, inexpensive technique for separating out these human olfactory stem cells and coaxing them to grow in a laboratory setting. If successful, this would pave the way for a human model that could be used to screen potential drugs designed to treat anosmia. Such a tool would be a game-changer for the millions of people worldwide living with a diminished sense of smell, providing a platform to test therapies that could one day restore a sense that is fundamental to the human experience.
