{"id":2684,"date":"2026-10-10T06:05:17","date_gmt":"2026-10-10T06:05:17","guid":{"rendered":"https:\/\/xesi.net\/?p=2684"},"modified":"2026-10-10T06:05:17","modified_gmt":"2026-10-10T06:05:17","slug":"breakthrough-three-dimensional-model-reveals-secrets-of-olfactory-regeneration-and-the-hidden-role-of-dormant-stem-cells","status":"publish","type":"post","link":"https:\/\/xesi.net\/?p=2684","title":{"rendered":"Breakthrough Three-Dimensional Model Reveals Secrets of Olfactory Regeneration and the Hidden Role of Dormant Stem Cells"},"content":{"rendered":"

Researchers at the Tufts University School of Medicine and the Graduate School of Biomedical Sciences (GSBS) have unlocked a critical piece of the puzzle regarding how the human nose repairs itself. Using a newly devised, three-dimensional tissue model, the team has discovered that a specific type of stem cell, long assumed to be dormant, actually plays a fundamental role in maintaining the sense of smell. This finding, published recently in Cell Reports Methods<\/em>, provides a sophisticated new lens through which scientists can view the regenerative capacity of the nasal cavity and potentially address the causes of sensory loss associated with aging, viral infections, and environmental toxins.<\/p>\n

Unlike the central nervous system, which possesses a notoriously limited ability to heal after injury, the sensory neurons within the nasal cavity exhibit a remarkable, lifelong capacity for regeneration. This ongoing renewal is essential, as these neurons are constantly exposed to the harsh, unpredictable external environment, including pathogens, pollutants, and irritants. However, this delicate balance can be disrupted. Viral infections\u2014most notably the widespread olfactory dysfunction seen during the COVID-19 pandemic\u2014as well as chronic exposure to toxins or the natural processes of biological aging, can diminish the function of these neurons or impair their ability to replicate. When this regenerative machinery falters, it can lead to a partial or total loss of smell, a condition that significantly impacts quality of life, nutritional intake, and safety.<\/p>\n

To better understand the biological mechanisms behind this failure, the Tufts research team, led by senior author Brian Lin, a research assistant professor in the Department of Developmental, Molecular and Chemical Biology, sought to create a more accessible research tool. They developed a new, easy-to-create, three-dimensional olfactory tissue mouse model, or organoid. This "mini-organ" platform allows scientists to observe, in real-time, the intricate processes by which neurons are continuously formed within the nasal epithelium and, perhaps more importantly, to identify the precise points at which these processes begin to decline in the face of disease or senescence.<\/p>\n

The research focuses on the interaction between two distinct populations of stem cells found within the nose: horizontal basal cells (HBCs) and globose basal cells (GBCs). Traditionally, the scientific community has viewed these cells as having very different levels of activity, with HBCs often characterized as a reserve pool that remains largely dormant until triggered by severe injury. However, the Tufts study suggests that this binary view may be overly simplistic.<\/p>\n

"Our research suggests that these two stem cells may be interdependent," explains Dr. Lin. "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 three-dimensional organoid model, the team identified a specific subpopulation of HBCs, which are distinguished by their expression of the protein KRT5. The researchers observed that these KRT5-positive HBCs are not merely passive bystanders waiting for catastrophic damage; rather, they are active participants in the routine generation of new olfactory neurons. When the team selectively depleted these specific HBCs from the organoid cultures, the regenerative capacity of the tissue was significantly impaired, confirming that these cells are essential players in the maintenance of the olfactory system.<\/p>\n

The study further investigated how this regenerative process changes over time. By comparing cells derived from mice of different ages and cultivating them within the organoid model, the researchers observed a clear, age-related decline in the ability 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

An Accessible Tool for Global Research<\/h3>\n

A significant portion of the project\u2019s success is attributed to the accessibility of the model itself. The lead author of the study, Juliana Gutschow Gameiro, a former Ph.D. student visiting GSBS from the State University of Londrina in Brazil, played a pivotal role in the model’s design. Dr. Lin emphasizes that Gameiro was deeply committed to developing a protocol that would be straightforward and affordable for laboratories with limited funding or specialized equipment.<\/p>\n

The urgency of this work has been underscored by recent global health events. As cases of persistent olfactory loss linked to COVID-19 have surged, the field of sensory biology has seen a sudden influx of interest. "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.<\/p>\n

By creating a simplified organoid model, the Tufts team hopes to democratize this research, allowing scientists who are not specialized stem cell biologists\u2014and those working in resource-constrained environments\u2014to investigate the mysteries of the olfactory system. Understanding the specific failures that lead to permanent anosmia, or loss of smell, is the first step toward developing therapeutic interventions that could one day restore this critical sense for millions of people worldwide.<\/p>\n

Bridging the Gap: The Quest for Human Organoids<\/h3>\n

The ultimate ambition of the research team is to transition from a mouse-tissue model to a human organoid. Such a tool would serve as a powerful platform for drug screening, allowing researchers to test potential treatments for olfactory loss in a controlled, human-derived environment. Organoids provide a distinct advantage over existing methods, as they offer a more accurate biological representation than traditional cell cultures while avoiding the ethical and logistical complexities associated with large-scale animal testing. While organoids have been successfully developed for other organs, such as the lungs and kidneys, human olfactory tissue remains a particularly stubborn frontier.<\/p>\n

"It’s challenging to get pure olfactory tissue from humans," Lin admits, pointing to the technical hurdles inherent in current collection methods. During clinical procedures, individuals are anesthetized, and a brush\u2014similar in appearance to a COVID-19 test swab\u2014is inserted deep into the nasal cavity to collect cells. Unlike the mouse model, where stem cell populations can be isolated with greater precision, human tissue samples gathered in this manner are often a mixture of respiratory and olfactory stem cells, which are notoriously difficult to separate.<\/p>\n

This separation process is the next major challenge for the team. The researchers are currently working to develop a technique that is both simple and inexpensive, which would allow them to isolate human olfactory stem cells and successfully coax them to grow and thrive in a lab setting. By perfecting this technique, they hope to unlock a new era of research where the regenerative potential of the human nose can be fully understood, managed, and eventually, harnessed to heal the damage caused by illness and time. Through this methodical approach, the team is moving closer to providing a long-awaited solution for those whose world has been muted by the loss of their sense of smell.<\/p>\n","protected":false},"excerpt":{"rendered":"

Researchers at the Tufts University School of Medicine and the Graduate School of Biomedical Sciences (GSBS) have unlocked a critical piece of the puzzle regarding how the human nose repairs itself. Using a newly devised, three-dimensional tissue model, the team has discovered that a specific type of stem cell, long assumed to be dormant, actually […]<\/p>\n","protected":false},"author":1,"featured_media":2683,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[650],"tags":[1823,2672,4405,4385,652,451,2485,656,4753,1166,666,1647,3379,2671,270,651],"class_list":["post-2684","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-health-and-wellness","tag-breakthrough","tag-cells","tag-dimensional","tag-dormant","tag-fitness","tag-health","tag-hidden","tag-model","tag-olfactory","tag-regeneration","tag-reveals","tag-role","tag-secrets","tag-stem","tag-three","tag-wellness"],"_links":{"self":[{"href":"https:\/\/xesi.net\/index.php?rest_route=\/wp\/v2\/posts\/2684","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=2684"}],"version-history":[{"count":0,"href":"https:\/\/xesi.net\/index.php?rest_route=\/wp\/v2\/posts\/2684\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/xesi.net\/index.php?rest_route=\/wp\/v2\/media\/2683"}],"wp:attachment":[{"href":"https:\/\/xesi.net\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=2684"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/xesi.net\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=2684"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/xesi.net\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=2684"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}