Next Step: A Human Organoid
While the mouse model has provided invaluable insights into the basic biology of the nose, the ultimate prize is the development of a human olfactory organoid. Such a tool would revolutionize the way we treat anosmia and other sensory disorders.
In the current pharmaceutical pipeline, drug testing often relies on animal models or two-dimensional human cell cultures, neither of which perfectly replicates the complex, 3D environment of the human body. Organoids—already successfully developed for the lungs, kidneys, and brain—bridge this gap, offering a more accurate platform for pre-clinical trials. They are faster, less expensive, and potentially more predictive of human responses than whole-animal testing.
However, creating a human version of the olfactory organoid presents unique logistical hurdles. Unlike mice, from whom tissue can be harvested relatively easily in a controlled environment, obtaining pure olfactory tissue from human subjects is a delicate and invasive procedure.
"It’s challenging to get pure olfactory tissue from humans," Lin explains. To collect the necessary cells, individuals must be anesthetized while a specialized brush—resembling a long-handled COVID-19 test swab—is inserted deep into the nasal vault to reach the olfactory epithelium. The primary difficulty arises after the collection: the sample is often a mixture of respiratory stem cells (which line the majority of the nose) and the specific olfactory stem cells needed for the organoid.
Unlike the mouse model, where these cell types are more easily distinguished, human respiratory and olfactory stem cells collected via brushing are difficult to separate. The Tufts team is now focusing their efforts on developing a simple, cost-effective technique to isolate these human olfactory stem cells and "coax" them into growing into functional 3D tissue in the lab.
If successful, this human organoid would serve as a high-throughput screening tool. Researchers could take a patient’s own cells, grow an organoid, and then test an array of medications to see which ones effectively stimulate neuron growth for that specific individual. This move toward personalized medicine could offer hope to those suffering from long-term smell loss, whether caused by the lingering effects of a virus, the toxic side effects of chemotherapy, or the inevitable march of time.
By uncovering the secret life of "dormant" stem cells and providing a new tool for the global scientific community, the researchers at Tufts are not just mapping the nose—they are laying the groundwork for a future where the loss of a sense is no longer a permanent sentence.
