Researchers at Tufts University School of Medicine and the Graduate School of Biomedical Sciences (GSBS) have unveiled a groundbreaking three-dimensional model designed to study the regeneration of nerve tissue within the human nose. This innovative approach has led to a significant discovery: a specific type of stem cell, previously dismissed as largely dormant, may be the unsung hero responsible for maintaining our sense of smell.<\/p>\n
Unlike the cells found in the central nervous system, which are notoriously difficult to repair once damaged, the sensory neurons lining the nasal cavity possess a remarkable, lifelong capacity for regeneration. This ability allows humans to recover their sense of smell even after frequent, direct exposure to environmental toxins, pollutants, and pathogens. However, this regenerative process is not infallible. Viral infections\u2014most notably the COVID-19 pandemic\u2014along with chronic exposure to harmful substances and the natural, inevitable process of biological aging, can impair these neurons. When these cells lose their ability to replicate or function correctly, the result is often a partial or complete loss of smell, a condition that can profoundly impact a person\u2019s quality of life, nutritional health, and psychological well-being.<\/p>\n
To better understand the mechanics of this regeneration and why it falters over time, a research team led by experts at Tufts devised a new, accessible, three-dimensional olfactory tissue mouse model. Their findings, published recently in the journal Cell Reports Methods<\/em>, provide a clear window into the complex communication network between two critical types of nasal stem cells: horizontal basal cells (HBCs) and globose basal cells (GBCs).<\/p>\n The study suggests that the interplay between these two stem cell populations is far more interdependent than previously hypothesized. Brian Lin, a research assistant professor in the Department of Developmental, Molecular and Chemical Biology and the study\u2019s senior author, explains that the research challenges long-standing assumptions about the dormancy of HBCs.<\/p>\n "Our research suggests that these two stem cells may be interdependent," says 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 their newly developed 3D organoid model, the team identified a distinct subpopulation of HBCs, characterized by their expression of the protein KRT5. These cells do not merely sit idle; rather, they actively facilitate the generation of new olfactory neurons. The researchers demonstrated that these KRT5-expressing HBCs are fundamental to the structural integrity and growth of the organoids. In experimental trials, when these specific cells were selectively depleted from the cultures, the organoids\u2019 ability to produce new neurons was drastically compromised. This evidence cements the status of these previously overlooked cells as essential players in the regenerative life cycle of the nose.<\/p>\n The researchers also explored the impact of aging on this regenerative capacity. By comparing cells taken from mice of varying ages, the team observed a clear decline in the ability of older cells to generate new neurons. Lin posits that this loss of function is linked to a reduction in the GBC population as the organism ages. "We think this is due to a decrease in the GBC population as we age," Lin notes, "but we need to do more work to test this hypothesis and, if so, develop ways to rejuvenate them."<\/p>\n A primary goal for the research team was to ensure that this model was not only scientifically rigorous but also practical for the broader scientific community. Juliana Gutschow Gameiro, the study\u2019s lead author and a former Ph.D. student visiting GSBS from the State University of Londrina in Brazil, played a pivotal role in refining the model. Her dedication to the project stemmed from a desire to create a system that could be easily replicated in laboratories, even those operating with limited funding or specialized equipment.<\/p>\n This accessibility is particularly timely. The global surge in interest regarding olfactory health, driven largely by the prevalence of smell loss following COVID-19 and its documented association with neurodegenerative conditions like Parkinson\u2019s disease, has brought a influx of new researchers into the field. <\/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 says. "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 team\u2019s 3D organoid model serves as a "living laboratory," allowing scientists to observe the cellular dynamics of the nose in a controlled environment. By democratizing access to this technology, the Tufts researchers hope to accelerate the pace of discovery regarding the underlying causes of anosmia and other olfactory deficits.<\/p>\n The long-term objective of this research is to move beyond mouse models and establish a human olfactory organoid. Such a tool would be invaluable for pre-clinical drug screening, offering a faster, more cost-effective, and potentially more accurate method for testing therapies than relying on whole-animal models or traditional human cell cultures. <\/p>\n Organoids\u2014miniature, simplified versions of organs grown in the lab\u2014have already transformed the study of lungs, kidneys, and other bodily systems. However, creating an organoid specifically for human olfactory tissue remains a significant technical hurdle.<\/p>\n "It’s challenging to get pure olfactory tissue from humans," Lin explains. The current clinical procedure involves anesthetizing a patient and using a brush\u2014similar to the ones used for COVID-19 nasal swabs\u2014to collect cells from deep within the nasal cavity. The primary complication, according to Lin, is the difficulty of separating human olfactory stem cells from respiratory stem cells collected during the same procedure. The respiratory cells are often far more abundant, which can overwhelm the olfactory stem cells in a culture.<\/p>\n The team\u2019s next major scientific challenge is to develop a technique that is both simple and inexpensive to effectively isolate these specific human olfactory stem cells from the mixture of other nasal cells. Once this isolation technique is perfected, the researchers hope to coax these cells to grow reliably in the laboratory setting. <\/p>\n If successful, the development of a human olfactory organoid could provide a revolutionary platform for personalized medicine. Researchers could theoretically grow a patient’s own olfactory cells in the lab to test how they respond to various pharmaceutical compounds, potentially identifying treatments that could restore the sense of smell for those suffering from chronic or post-viral loss. <\/p>\n As the research team continues to refine their 3D models and investigate the complex signaling pathways between HBCs and GBCs, the possibility of therapeutic intervention for olfactory loss becomes increasingly tangible. By uncovering the "hidden" potential of previously dormant stem cells, this work offers new hope for the millions of people worldwide currently living with a diminished sense of smell.<\/p>\n","protected":false},"excerpt":{"rendered":" Researchers at Tufts University School of Medicine and the Graduate School of Biomedical Sciences (GSBS) have unveiled a groundbreaking three-dimensional model designed to study the regeneration of nerve tissue within the human nose. This innovative approach has led to a significant discovery: a specific type of stem cell, previously dismissed as largely dormant, may be […]<\/p>\n","protected":false},"author":1,"featured_media":2503,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[650],"tags":[2672,4405,652,451,2485,656,2673,666,1647,658,659,2671,270,651],"class_list":["post-2504","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-health-and-wellness","tag-cells","tag-dimensional","tag-fitness","tag-health","tag-hidden","tag-model","tag-restoring","tag-reveals","tag-role","tag-sense","tag-smell","tag-stem","tag-three","tag-wellness"],"_links":{"self":[{"href":"https:\/\/xesi.net\/index.php?rest_route=\/wp\/v2\/posts\/2504","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=2504"}],"version-history":[{"count":0,"href":"https:\/\/xesi.net\/index.php?rest_route=\/wp\/v2\/posts\/2504\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/xesi.net\/index.php?rest_route=\/wp\/v2\/media\/2503"}],"wp:attachment":[{"href":"https:\/\/xesi.net\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=2504"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/xesi.net\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=2504"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/xesi.net\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=2504"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}Unlocking the Mystery of Nasal Regeneration<\/h3>\n
An Accessible Model for Global Research<\/h3>\n
The Path Toward Human Organoids<\/h3>\n