Next Step: A Human Organoid
While the current mouse-tissue model has provided groundbreaking insights, the Tufts team views it as a stepping stone toward a more ambitious goal: the creation of a human olfactory organoid. Such a model would be a game-changer for clinical medicine, providing a platform to screen drugs and develop therapies for patients suffering from permanent smell loss.
In the pharmaceutical industry, organoids represent a major leap forward. They allow for pre-clinical trials that are faster, less expensive, and often more accurate than traditional animal testing or 2D cell cultures. However, creating a human version of the olfactory model presents unique challenges.
The primary hurdle lies in the collection of pure tissue. In mice, researchers can easily access the necessary stem cells. In humans, the process is far more invasive and technically difficult. Currently, obtaining olfactory tissue requires a patient to be anesthetized while a specialized brush—similar to a long COVID-19 testing swab—is inserted deep into the nasal cavity to harvest cells.
"It’s challenging to get pure olfactory tissue from humans," Lin notes. The procedure often results in a mixture of different cell types. Unlike the mouse model, where the researchers can precisely isolate the necessary components, human samples often contain a blend of respiratory stem cells and olfactory stem cells that are difficult to untangle.
The research team’s next challenge is to bridge this gap. They are working to develop a simple, cost-effective technique to separate human olfactory stem cells from their respiratory counterparts and "coax" them into growing into 3D organoids in the lab. If successful, this would allow doctors to take a small sample from a patient, grow their specific nasal tissue in a dish, and test which treatments or medications might best restore their sense of smell.
As the scientific community continues to grapple with the long-term effects of viral infections and the challenges of an aging population, the work at Tufts University offers a promising path forward. By revealing the hidden activity of "dormant" cells and providing the tools to study them, researchers are moving closer to a future where the loss of smell is no longer a permanent sentence, but a treatable condition.
