Next Step: A Human Organoid
While the mouse model has provided invaluable insights into the basic mechanics of stem cell interdependency, the ultimate objective of the Tufts researchers is to translate these findings into human health solutions. The next phase of their work involves the transition from mouse tissue to human tissue, with the goal of creating a human olfactory organoid.
The potential for a human-based model is vast. Such an organoid could serve as a high-throughput screening platform for new drugs, allowing scientists to test potential treatments for anosmia or hyposmia (reduced sense of smell) in a lab setting before moving to clinical trials. This would make the drug development process faster, less expensive, and more accurate than current methods, which often rely on whole-animal testing or simplified 2D cell cultures that fail to capture the 3D complexity of human tissue.
However, the path to a human organoid is fraught with technical challenges. One of the primary hurdles is the difficulty of obtaining high-quality, pure olfactory tissue from human subjects.
"It’s challenging to get pure olfactory tissue from humans," Lin notes. Currently, the process of collecting these cells is invasive and uncomfortable. Patients must be anesthetized while a specialized brush—similar in shape to the swabs used for COVID-19 testing but designed to reach much deeper—is inserted high into the nasal cavity to harvest cells from the olfactory epithelium.
A complicating factor is that the human nose is a mixture of different tissue types. The brush often collects a combination of respiratory stem cells and olfactory stem cells. Unlike the mouse model, where these populations are more easily distinguished, human respiratory and olfactory cells are difficult to isolate from one another in a lab setting.
The research team’s next major challenge is to refine the "recipe" for the human model. They are working to develop a simple, cost-effective technique that can separate these human olfactory stem cells from their respiratory neighbors and "coax" them into growing and differentiating within the 3D organoid structure.
If successful, the creation of a human olfactory organoid would represent a major milestone in regenerative medicine. It would not only provide a window into the unique ways the human nose responds to viruses like SARS-CoV-2 or the early stages of neurodegenerative diseases like Parkinson’s—where loss of smell is often one of the earliest clinical signs—but also offer a platform for the next generation of sensory therapies. For now, the Tufts study stands as a vital reminder that even the cells we once thought were "sleeping" may hold the key to our most essential biological functions.
