The Unexpected Key to Restoring Your Sense of Smell May Lie in ‘Dormant’ Stem Cells
Over 5 million adults in the US experience a loss of smell, a condition linked to everything from COVID-19 and neurodegenerative diseases like Parkinson’s, to simply the natural aging process. But a new breakthrough from Tufts University is challenging long-held beliefs about how our noses regenerate, suggesting a previously overlooked type of stem cell could hold the key to restoring this vital sense. Researchers have developed a remarkably accessible new model for studying olfactory regeneration, paving the way for potential therapies and a deeper understanding of how – and why – we lose our sense of smell.
A New Model for Olfactory Regeneration
For decades, scientists believed that globose basal cells (GBCs) were the primary drivers of new neuron growth in the nasal cavity. Unlike neurons in the brain, those responsible for smell have a unique ability to regenerate throughout life. However, this process can be disrupted by viral infections, toxins, and age. The Tufts team, led by Brian Lin, has now demonstrated that horizontal basal cells (HBCs) – previously considered largely inactive – play a crucial supporting role. Their innovation? A three-dimensional olfactory tissue ‘organoid’ grown from mouse cells, offering a simplified and cost-effective way to study this complex process.
The Role of KRT5+ HBCs
This isn’t just about discovering a new player; it’s about understanding how these cells interact. The researchers identified a specific subpopulation of HBCs, marked by the protein KRT5, that are actively involved in supporting the creation of new olfactory neurons. When these KRT5+ HBCs were selectively removed from the organoid cultures, neuron generation significantly decreased. This finding fundamentally shifts our understanding of olfactory regeneration, highlighting the interdependence of HBCs and GBCs.
Aging and the Decline of Smell: A GBC Connection?
The research also sheds light on why our sense of smell diminishes with age. By growing cells from older mice in the organoid model, the team observed a reduced capacity for neuron generation. While further research is needed, the initial data suggests a decline in the GBC population as we age may be a key factor. This opens up exciting possibilities for developing interventions to rejuvenate these cells and potentially restore lost olfactory function. “We need to do more work to test this hypothesis and, if so, develop ways to rejuvenate them,” explains Lin.
Why This Model Matters: Accessibility and Affordability
One of the most significant aspects of this research isn’t just the biological discovery, but the accessibility of the model itself. Lead author Juliana Gutschow Gameiro prioritized creating a system that could be easily replicated in labs with limited resources. This is particularly important given the surge in olfactory research spurred by the COVID-19 pandemic and the growing recognition of smell loss as an early indicator of neurological disorders like Parkinson’s disease. As Lin notes, “We wanted to develop an easy-to-use model so that non-stem cell biologists…could use it to better understand how olfactory neurons regenerate.”
The Future: Human Organoids and Drug Screening
The mouse model is just the first step. The ultimate goal is to translate this research into a human organoid – a miniature, lab-grown version of human olfactory tissue. This would allow scientists to screen potential drugs for their ability to restore smell function in individuals suffering from anosmia (loss of smell) or hyposmia (reduced sense of smell). Organoids offer a faster, cheaper, and potentially more effective alternative to traditional animal testing and human cell cultures.
However, creating a human olfactory organoid presents its own challenges. Obtaining pure olfactory tissue from humans is difficult, requiring a procedure similar to a COVID test swab. Separating the olfactory stem cells from other respiratory cells within that sample is a complex process. The team is now focused on developing a simple and inexpensive technique to overcome this hurdle.
This research represents a significant leap forward in our understanding of olfactory regeneration. By challenging existing paradigms and providing a powerful new research tool, the Tufts team is paving the way for potential therapies that could restore a fundamental sense for millions of people. What are your predictions for the future of smell restoration therapies? Share your thoughts in the comments below!