Researchers at Tufts University School of Medicine and the Graduate School of Biomedical Sciences (GSBS) have unveiled a significant discovery that challenges long-held assumptions about the human sense of smell. By utilizing a newly devised, three-dimensional model to observe the regeneration of nerve tissue within the nose, the team has identified that a specific type of stem cell, previously believed to be largely dormant, plays a far more active and essential role in preserving olfactory function than scientists had ever suspected.<\/p>\n
This finding offers a promising new avenue for understanding why millions of people lose their sense of smell due to viral infections, environmental toxins, or the natural process of aging. The research, recently published in the journal Cell Reports Methods<\/em>, details how these stem cells orchestrate the complex repair of nasal tissue, providing a clearer picture of the biological mechanisms that keep our olfactory system resilient throughout our lives.<\/p>\n The human olfactory system is a biological anomaly. Unlike the central nervous system, which possesses a notoriously limited capacity for repair, the sensory neurons within the nasal cavity exhibit a remarkable and consistent ability to regenerate. Throughout an individual\u2019s life, these neurons are exposed to the harsh, unpredictable conditions of the outside world\u2014inhaling pollutants, pathogens, and various chemicals\u2014yet they maintain the capacity to replicate and replace damaged cells.<\/p>\n However, this regenerative process is not infallible. When the system is overwhelmed by severe viral infections, such as COVID-19, or subjected to chronic exposure to environmental toxins, the ability of these cells to function or replicate can be severely diminished. Furthermore, the natural aging process inherently slows down this cellular turnover. When the delicate balance of regeneration is disrupted, the result is often a partial or complete loss of smell, a condition known as anosmia, which can profoundly affect an individual’s quality of life, safety, and psychological well-being.<\/p>\n To better investigate why this regenerative process falters, the Tufts research team developed an innovative tool: a three-dimensional olfactory tissue mouse model, or organoid. By creating this "mini-organ" in the lab, scientists can observe the intricate cellular dynamics of the nose in a controlled, replicable environment, helping to pinpoint exactly where and why the production of new neurons fails as disease or age takes its toll.<\/p>\n The study centers on the interaction between two distinct types of stem cells found within the nose: horizontal basal cells (HBCs) and globose basal cells (GBCs). Through the lens of their new 3D model, the researchers observed that these two cell types do not act in isolation. Instead, they communicate and support one another in a symbiotic relationship to develop new smell-sensing nerve tissue.<\/p>\n "Our research suggests that these two stem cells may be interdependent," says Brian Lin, senior author on the study and a research assistant professor in the Department of Developmental, Molecular and Chemical Biology at Tufts University. "One type that we thought was largely dormant\u2014HBCs\u2014may actually play a crucial role in supporting the production of new neurons and the repair of damaged tissue."<\/p>\n By examining the organoids, the team successfully identified a specific subpopulation of HBCs, which are distinguished by their production of the protein KRT5. These cells were found to be active participants in the generation of new olfactory neurons. When the researchers experimentally depleted these KRT5-marked HBCs from the organoid cultures, the formation of new neurons was significantly impaired. This observation confirmed that these cells are not merely bystanders or "reserve" cells waiting for a catastrophic injury; they are essential, active players in the ongoing maintenance and regenerative capacity of the nose.<\/p>\n The researchers also extended their investigation to compare cells derived from mice of different ages. By growing these cells within their 3D model, they observed a distinct decline in the ability of older cells to generate new neurons. "We found a decline in the ability of the older mice cells to generate new neurons," Lin notes. "We think this is due to a decrease in the GBC population as we age, but we need to do more work to test this hypothesis and if so, develop ways to rejuvenate them."<\/p>\n A significant portion of the study\u2019s success lies in the accessibility of the model itself. Juliana Gutschow Gameiro, the lead author of the study and a former Ph.D. student visiting GSBS from the State University of Londrina in Brazil, focused her efforts on ensuring that the organoid model could be constructed using resources available to labs with limited funding and equipment.<\/p>\n The urgency of this work has been underscored by the global impact of COVID-19, which frequently presents with a loss of smell as a primary symptom. As the medical community grapples with the long-term consequences of such infections, as well as the olfactory decline associated with neurodegenerative conditions like Parkinson’s disease, the demand for high-quality, reproducible research tools has skyrocketed.<\/p>\n "Because loss of smell is associated with COVID-19, as well as with Parkinson’s disease and other conditions, a much larger number of researchers from a variety of different fields have begun researching olfactory epithelial cells in the last few years," says Lin. "We wanted to develop an easy-to-use model so that non-stem cell biologists and those working in labs with limited resources could use it to better understand how olfactory neurons regenerate and what happens that causes that process to diminish or fail completely."<\/p>\n By lowering the barrier to entry, the Tufts team hopes to catalyze a broader, more collaborative effort across the scientific community to study the nose. By democratizing access to this 3D model, they hope to facilitate faster breakthroughs in regenerative medicine.<\/p>\n The long-term vision for the research team is to evolve this mouse-tissue model into a human organoid. Such a tool would be invaluable for pre-clinical drug screening, allowing researchers to test therapeutic interventions in a human context before moving to clinical trials. The goal is to develop treatments that could restore or enhance the sense of smell for patients suffering from persistent anosmia.<\/p>\n Organoids offer a distinct advantage over existing methods of research. They are faster, significantly less expensive, and potentially more effective than using whole animal models or traditional human cell cultures, which often fail to replicate the complex, three-dimensional architecture of living tissue. While scientists have successfully developed organoids for other organs, such as the lungs and kidneys, human olfactory tissue remains a challenging frontier.<\/p>\n "It’s challenging to get pure olfactory tissue from humans," Lin explains. The standard collection method\u2014involving a brush similar to a COVID-19 test swab inserted deep into the nasal cavity\u2014is invasive and results in a mixture of tissue types. "Unlike in their mouse model, human respiratory stem cells and olfactory stem cells collected in this process are difficult to separate."<\/p>\n Overcoming this hurdle is the next major challenge for the Tufts team. Their objective is to refine a technique that is both simple and inexpensive, allowing them to isolate human olfactory stem cells from other nasal tissues and coax them into growth within the laboratory. By successfully cultivating human olfactory organoids, the researchers believe they can open the door to a new era of personalized medicine, where the biological mysteries of the sense of smell are no longer hidden, but accessible for study and therapeutic intervention.<\/p>\n","protected":false},"excerpt":{"rendered":" Researchers at Tufts University School of Medicine and the Graduate School of Biomedical Sciences (GSBS) have unveiled a significant discovery that challenges long-held assumptions about the human sense of smell. By utilizing a newly devised, three-dimensional model to observe the regeneration of nerve tissue within the nose, the team has identified that a specific type […]<\/p>\n","protected":false},"author":1,"featured_media":2294,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[650],"tags":[1823,2672,652,451,527,656,3893,2673,666,1647,667,658,659,2671,651],"class_list":["post-2295","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-health-and-wellness","tag-breakthrough","tag-cells","tag-fitness","tag-health","tag-life","tag-model","tag-nasal","tag-restoring","tag-reveals","tag-role","tag-secret","tag-sense","tag-smell","tag-stem","tag-wellness"],"_links":{"self":[{"href":"https:\/\/xesi.net\/index.php?rest_route=\/wp\/v2\/posts\/2295","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/xesi.net\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/xesi.net\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/xesi.net\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/xesi.net\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=2295"}],"version-history":[{"count":0,"href":"https:\/\/xesi.net\/index.php?rest_route=\/wp\/v2\/posts\/2295\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/xesi.net\/index.php?rest_route=\/wp\/v2\/media\/2294"}],"wp:attachment":[{"href":"https:\/\/xesi.net\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=2295"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/xesi.net\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=2295"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/xesi.net\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=2295"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}The Remarkable Resilience of the Olfactory System<\/h3>\n
Deciphering the Roles of Nasal Stem Cells<\/h3>\n
An Accessible Tool for Global Research<\/h3>\n
The Path Toward Human Organoids<\/h3>\n