Innovative 3D Model Sheds New Light on How the Sense of Smell Regenerates and Fades
Scientists at Tufts University School of Medicine and the Graduate School of Biomedical Sciences (GSBS), alongside an international team of researchers, have engineered a novel three-dimensional model to investigate nerve tissue regeneration within the nose. Published in *Cell Reports Methods*, the study challenges long-held assumptions regarding olfactory stem cells. Specifically, the findings indicate that a specific population of stem cells once thought to be completely dormant actually plays a critical, active role in preserving and repairing the human or mammalian sense of smell.
Unlike neurons found in the central nervous system, sensory neurons inside the nasal cavity possess a unique capacity to continually regenerate throughout life, even though they endure near-constant exposure to external environmental factors. However, viral infections such as COVID-19, environmental toxins, and natural biological aging can compromise this regenerative process, resulting in a partial or total loss of smell. To explore why these sensory structures falter, the Tufts team designed an affordable, highly accessible 3D mouse olfactory organoid model. This simplified system enables investigators to watch firsthand how nerve-sensing tissue forms and why repair mechanisms ultimately decline.
Within the nasal tissue, two primary types of stem cells work together: horizontal basal cells (HBCs) and globose basal cells (GBCs). Prior to this investigation, conventional scientific understanding held that HBCs remained mostly inactive under normal circumstances. However, senior study author Brian Lin, a research assistant professor in the Department of Developmental, Molecular and Chemical Biology at Tufts, noted that these cell populations are actually interdependent. The team identified a distinct subpopulation of HBCs, characterized by the production of the protein KRT5, which actively supports the generation of brand-new olfactory neurons. When the researchers selectively depleted these KRT5-producing HBCs from their organoid cultures, the formation of new neurons dropped sharply, confirming that these once-dismissed cells are vital components of tissue repair.
To better understand age-related sensory decline, the research team cultivated cells harvested from mice of varying ages inside the 3D model. Their observations revealed a noticeable reduction in the capacity of older cells to generate new neurons. The investigators hypothesize that this drop stems from a depletion of the GBC population over time, though further studies are required to confirm this mechanism and explore potential methods to rejuvenate aging cellular populations.
Lead author Juliana Gutschow Gameiro, a visiting Ph.D. student who came to Tufts from the State University of Londrina in Brazil, focused heavily on ensuring the experimental model could be easily replicated in laboratories with limited funding and equipment. Because conditions like Parkinson’s disease, long-term aging, and viral infections frequently disrupt olfactory function, a broader community of scientists from diverse specialties has started examining nasal epithelial tissue. By making the experimental setup affordable and user-friendly, the Tufts team hopes to accelerate global research into the underlying biological failures of smell loss.
The ultimate objective for the research group is to translate this mouse-based tissue platform into a human organoid model. Human olfactory organoids could eventually serve as efficient pre-clinical screening tools for novel therapeutics aimed at restoring olfactory function in patients. However, obtaining pure human olfactory tissue remains a significant technical hurdle. Clinicians typically collect nasal cells via a swab during deep nasal examinations, but human respiratory and olfactory stem cells are difficult to isolate from one another using standard approaches. Consequently, the next phase of the research initiative will concentrate on developing a simple, cost-effective protocol to separate human olfactory stem cells and successfully propagate them in a laboratory environment.
Source: ScienceDaily Health & Medicine