A team of researchers at Tufts University School of Medicine and the Graduate School of Biomedical Sciences (GSBS) has unveiled a significant breakthrough in our understanding of how the nose maintains its sense of smell. By developing an innovative three-dimensional organoid model, the scientists have discovered that a specific type of stem cell, previously assumed to be largely dormant, plays a far more active and essential role in the regeneration of olfactory nerve tissue than was ever anticipated.<\/p>\n
This discovery sheds new light on the mechanisms governing the nasal cavity\u2019s unique ability to repair itself. Unlike the central nervous system, where neuronal damage is often permanent and catastrophic, the sensory neurons responsible for smell possess a remarkable capacity for regeneration throughout an individual\u2019s lifespan. This is a vital evolutionary adaptation, as these neurons are in constant, direct contact with the external environment, leaving them uniquely vulnerable to inhaled toxins, pathogens, and environmental pollutants.<\/p>\n
However, this resilience is not infallible. Viral infections\u2014most notably those caused by the SARS-CoV-2 virus\u2014as well as chronic exposure to environmental toxins and the natural processes of aging can overwhelm the nasal cavity\u2019s regenerative machinery. When these sensory neurons are destroyed faster than they can be replaced, or when the stem cells responsible for their creation falter, individuals experience a partial or complete loss of smell, known as anosmia or hyposmia. To better investigate the underlying mechanics of this process, the Tufts team sought to create a more effective, accessible, and scalable experimental platform.<\/p>\n
The researchers, whose findings were recently published in Cell Reports Methods<\/em>, developed a three-dimensional olfactory tissue mouse model. These organoids\u2014miniature, simplified versions of organs grown in the laboratory\u2014allow scientists to observe in real-time how olfactory neurons are continuously generated and, crucially, why this regenerative cycle often fails in the context of disease or senescence.<\/p>\n Central to this study is the complex relationship between two specific types of stem cells found in the nasal epithelium: horizontal basal cells (HBCs) and globose basal cells (GBCs). For years, the prevailing scientific consensus held that GBCs were the primary engine of neuronal regeneration, while HBCs were viewed as a dormant reserve, activated only in extreme circumstances to repair severe tissue damage.<\/p>\n The Tufts study challenges this rigid hierarchy. Brian Lin, a research assistant professor in the Department of Developmental, Molecular and Chemical Biology and senior author of the study, explains that the two populations appear to be far more interconnected than previously recognized.<\/p>\n "Our research suggests that these two stem cells may be interdependent," Lin says. "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 utilizing their 3D model, the research team identified a specific subpopulation of HBCs, distinguished by the expression of the protein KRT5. These KRT5-positive cells were found to be active participants in the generation of new olfactory neurons. When the team performed experiments to selectively deplete these specific HBCs from the organoid cultures, the generation of new neurons was significantly impaired. This finding effectively reclassifies these cells from a passive reserve to an essential, active component of the regenerative process, providing a new target for potential therapeutic interventions.<\/p>\n The researchers also turned their attention to the effects of aging. By cultivating olfactory tissue from mice of different ages, the team was able to observe the degradation of regenerative capacity over time. "We found a decline in the ability of the older mice cells to generate new neurons," Lin observes. "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 The project was spearheaded by lead author Juliana Gutschow Gameiro, a visiting Ph.D. student from the State University of Londrina in Brazil. Her primary objective was not just to achieve a scientific breakthrough, but to ensure that the methodology was accessible to the broader research community. Recognizing that many laboratories operate under strict financial and equipment constraints, the team prioritized the development of an "easy-to-use" model that would lower the barrier to entry for studying olfactory regeneration.<\/p>\n This push for accessibility comes at a critical time in sensory research. The global emergence of COVID-19, which frequently causes olfactory dysfunction, has sparked a surge in interest among researchers across diverse disciplines. Conditions such as Parkinson\u2019s disease and other neurodegenerative disorders are also frequently preceded by a loss of smell, further heightening the urgency for standardized research tools.<\/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," Lin notes. "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 The success of the mouse-derived organoid is a significant step toward the long-term goal of the Tufts team: the creation of a human olfactory organoid. Such a tool would provide a powerful, efficient, and ethical platform for drug screening, potentially allowing for the rapid identification of treatments for patients suffering from persistent olfactory loss.<\/p>\n While organoid technology has already revolutionized research in other areas of human biology\u2014with established models for the lung, kidney, and liver\u2014the olfactory system has proven notoriously difficult to replicate in the lab. The primary hurdle remains the acquisition and isolation of pure human olfactory tissue.<\/p>\n Currently, the clinical process for obtaining such samples involves anesthesia and the use of a brush-like device, similar to a diagnostic COVID-19 test, to collect cells from deep within the nasal cavity. However, unlike the mouse model, the human samples obtained through this method contain a mixture of both respiratory stem cells and olfactory stem cells. Distinguishing between these two populations and successfully coaxing the olfactory stem cells to flourish in a laboratory environment remains a daunting technical challenge.<\/p>\n As the team looks toward the future, their focus is on refining the techniques required to isolate and cultivate human olfactory stem cells. By bridging the gap between their current mouse-based success and the potential for human applications, the researchers hope to unlock new pathways to restore sensory function, offering hope to millions of individuals whose lives have been impacted by the loss of their sense of smell. Through their commitment to developing scalable, accessible technology, the Tufts researchers are laying the groundwork for a new era of olfactory medicine.<\/p>\n","protected":false},"excerpt":{"rendered":" A team of researchers at Tufts University School of Medicine and the Graduate School of Biomedical Sciences (GSBS) has unveiled a significant breakthrough in our understanding of how the nose maintains its sense of smell. By developing an innovative three-dimensional organoid model, the scientists have discovered that a specific type of stem cell, previously assumed […]<\/p>\n","protected":false},"author":1,"featured_media":3147,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[650],"tags":[2672,4385,652,451,2485,3893,1166,653,1647,2671,1165,1160,651],"class_list":["post-3148","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-health-and-wellness","tag-cells","tag-dormant","tag-fitness","tag-health","tag-hidden","tag-nasal","tag-regeneration","tag-researchers","tag-role","tag-stem","tag-tissue","tag-uncover","tag-wellness"],"_links":{"self":[{"href":"https:\/\/xesi.net\/index.php?rest_route=\/wp\/v2\/posts\/3148","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=3148"}],"version-history":[{"count":0,"href":"https:\/\/xesi.net\/index.php?rest_route=\/wp\/v2\/posts\/3148\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/xesi.net\/index.php?rest_route=\/wp\/v2\/media\/3147"}],"wp:attachment":[{"href":"https:\/\/xesi.net\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=3148"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/xesi.net\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=3148"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/xesi.net\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=3148"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}The Interdependence of Nasal Stem Cells<\/h3>\n
A Model Designed for Accessibility<\/h3>\n