In a breakthrough that could reshape our understanding of how the human body repairs its sensory systems, researchers at Tufts University School of Medicine and the Graduate School of Biomedical Sciences (GSBS) have unveiled a sophisticated, three-dimensional model to study nerve tissue regeneration in the nose. This development has led to the surprising discovery that a specific type of stem cell, long dismissed by the scientific community as dormant, is actually a vital engine for maintaining the sense of smell.<\/p>\n
Unlike the cells of the central nervous system, which are notoriously difficult to repair once damaged, the sensory neurons located in the nasal cavity possess an extraordinary capacity for regeneration. Throughout a person\u2019s lifetime, these neurons are replaced, allowing the sense of smell to endure despite constant exposure to environmental hazards, pollutants, and pathogens. However, this regenerative process is not infallible. Viral infections\u2014most notably the COVID-19 pandemic\u2014as well as toxic chemical exposure and the natural progression of aging, can severely impair or even halt this replication process. The result is often a partial or complete loss of smell, a condition that can have profound impacts on a person\u2019s quality of life, nutritional health, and cognitive safety.<\/p>\n
To better understand why this biological repair mechanism falters, the research team, led by scientists at Tufts, developed an innovative 3D olfactory tissue mouse model, or organoid. By creating this "lab-grown" version of nasal tissue, the researchers have opened a new window into the cellular dynamics of smell, allowing them to observe in real-time how neurons are formed and where the system breaks down during disease or senescence. Their findings, which were recently published in the journal Cell Reports Methods<\/em>, provide a detailed look at the complex, collaborative relationship between two key populations of stem cells in the nose: horizontal basal cells (HBCs) and globose basal cells (GBCs).<\/p>\n The study highlights a sophisticated interdependency between these two stem cell types. Traditionally, GBCs were considered the primary workhorses of olfactory regeneration, while HBCs were categorized as "reserve" or "dormant" cells, waiting in the background to act only during catastrophic tissue injury. However, the Tufts study suggests that this view may have been overly simplistic.<\/p>\n "Our research suggests that these two stem cells may be interdependent," explains Brian Lin, a research assistant professor in the Department of Developmental, Molecular and Chemical Biology and the senior author of the study. "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 the 3D organoid model, the team successfully identified a specific subpopulation of HBCs, distinguished by their expression of the protein KRT5. These KRT5-positive cells were observed to be actively involved in the ongoing generation of new olfactory neurons, rather than remaining idle. To test the necessity of these cells, the researchers selectively depleted them from the organoid cultures. The result was a significant impairment in the formation of new neurons, confirming that these once-overlooked cells are, in fact, essential players in the maintenance of olfactory health.<\/p>\n The implications of this discovery extend to the field of aging research as well. As part of their study, the researchers cultivated tissue from mice of varying ages within the 3D model. They observed a clear, age-related decline in the ability of the cells to generate new neurons. Lin and his team hypothesize that this decline is linked to a reduction in the GBC population over time. While further investigation is required to confirm this mechanism and explore potential therapeutic interventions, the model provides the necessary framework to begin testing ways to "rejuvenate" these aging stem cell populations, potentially offering hope for reversing age-related olfactory loss.<\/p>\n A significant achievement of this research project is the accessibility of the model itself. The study was led by Juliana Gutschow Gameiro, a former Ph.D. student who visited the GSBS from the State University of Londrina in Brazil. A core goal for Gameiro was to design a system that could be easily replicated by laboratories around the world, including those with limited financial resources or specialized equipment.<\/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 simplifying the methodology for growing these organoids, the Tufts team hopes to catalyze a wider research effort. The current landscape of sensory research is often hampered by the difficulty of studying human nasal tissue, which is notoriously delicate and difficult to isolate. The mouse-tissue organoid serves as a crucial "proof of concept," demonstrating that complex regenerative pathways can be studied in a controlled, 3D environment without the ethical and logistical complexities of using whole animal models for every stage of testing.<\/p>\n The ultimate objective of the Tufts team is to translate this mouse-based success into a human organoid model. Such a tool would be a major leap forward in translational medicine, providing a reliable platform for high-throughput drug screening. Currently, pre-clinical research often relies on whole animal models, which are not only expensive and time-consuming but can also fail to accurately predict how human biology will react to a drug. Human organoids, by contrast, offer a more precise, ethical, and efficient pathway to identifying therapies for those suffering from chronic olfactory dysfunction.<\/p>\n While organoids have already been successfully developed for other organs, such as the lungs and kidneys, human olfactory tissue remains a difficult target. "It’s challenging to get pure olfactory tissue from humans," Lin explains. The standard collection procedure involves using a brush, similar to a COVID-19 testing swab, to sample cells deep within the nasal cavity. In humans, unlike in the mouse models the team has perfected, the stem cells responsible for regenerating the olfactory tissue are often intermingled with respiratory stem cells. Separating these two distinct populations remains a significant technical hurdle.<\/p>\n The team is now focusing their efforts on developing an inexpensive, reliable technique to isolate these human olfactory stem cells and coax them into growth in a laboratory setting. If they succeed, the impact could be far-reaching. As the global scientific community continues to grapple with the long-term sensory impacts of the COVID-19 pandemic and the increasing prevalence of neurodegenerative diseases where smell loss is an early symptom, the ability to study human olfactory regeneration in a dish will be an invaluable asset.<\/p>\n By shifting the focus toward the previously ignored HBCs and creating a robust, accessible model for further study, the Tufts University team has provided a new foundation for future regenerative therapies. As they move toward the development of human olfactory organoids, the possibility of restoring the sense of smell for millions of people worldwide moves one step closer to reality. The research serves as a poignant reminder that even the smallest, most overlooked cells can hold the key to restoring some of our most vital human functions.<\/p>\n","protected":false},"excerpt":{"rendered":" In a breakthrough that could reshape our understanding of how the human body repairs its sensory systems, researchers at Tufts University School of Medicine and the Graduate School of Biomedical Sciences (GSBS) have unveiled a sophisticated, three-dimensional model to study nerve tissue regeneration in the nose. This development has led to the surprising discovery that […]<\/p>\n","protected":false},"author":1,"featured_media":2106,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[650],"tags":[2672,652,451,527,656,3893,2673,666,1647,667,658,659,2671,651],"class_list":["post-2107","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-health-and-wellness","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\/2107","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=2107"}],"version-history":[{"count":0,"href":"https:\/\/xesi.net\/index.php?rest_route=\/wp\/v2\/posts\/2107\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/xesi.net\/index.php?rest_route=\/wp\/v2\/media\/2106"}],"wp:attachment":[{"href":"https:\/\/xesi.net\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=2107"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/xesi.net\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=2107"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/xesi.net\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=2107"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}Unlocking the Potential of ‘Dormant’ Cells<\/h3>\n
A Democratized Tool for Research<\/h3>\n
Paving the Way for Human Organoids<\/h3>\n