Researchers at the Tufts University School of Medicine and the Graduate School of Biomedical Sciences (GSBS) have unlocked a new understanding of how the human nose maintains its sense of smell, identifying a previously underestimated stem cell population that plays a critical role in tissue repair. By engineering a novel, three-dimensional model to study the regeneration of nerve tissue, the team has challenged long-standing assumptions about cellular dormancy and opened new pathways for treating the loss of smell, a condition that has become increasingly prevalent in the wake of the COVID-19 pandemic.<\/p>\n
Unlike most regions of the central nervous system, where neuronal damage is often permanent, the sensory neurons within the nasal cavity possess a remarkable, lifelong capacity for regeneration. Despite being in constant, direct contact with the external environment\u2014a volatile space filled with pathogens, toxins, and environmental pollutants\u2014the nose is capable of replacing damaged olfactory neurons throughout an individual\u2019s life. However, this regenerative engine can falter. Viral infections, chronic exposure to environmental toxins, and the natural progression of biological aging can all diminish the functionality of these cells, leading to a partial or total loss of smell, known as anosmia. <\/p>\n
To better understand the mechanisms governing this renewal and the reasons why it eventually declines, a team of researchers led by Tufts scientists developed a highly accessible, three-dimensional olfactory tissue mouse model. This organoid, detailed in a recent publication in Cell Reports Methods<\/em>, provides a sophisticated yet practical platform for observing the complex cellular dialogue that occurs during the birth of new neurons.<\/p>\n The research centers on two distinct types of stem cells residing within the nasal epithelium: horizontal basal cells (HBCs) and globose basal cells (GBCs). Traditionally, the scientific consensus viewed GBCs as the primary workhorses of neurogenesis, while HBCs were categorized as a largely dormant reserve pool, activated only in the event of severe injury to the nasal lining. <\/p>\n However, the findings from the Tufts team suggest a far more nuanced and interdependent relationship. "Our research suggests that these two stem cells may be interdependent," explains Brian Lin, senior author on the study and a research assistant professor in the Department of Developmental, Molecular and Chemical Biology at Tufts. "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 Through their three-dimensional organoid model, the researchers identified a specific subpopulation of HBCs, distinguished by their expression of the protein KRT5. This subpopulation does not merely wait for catastrophic damage; rather, it actively contributes to the routine generation of new olfactory neurons. By selectively depleting these KRT5-positive HBCs from the organoid cultures, the team observed a significant impairment in the generation of new nerve tissue. The experiment provided clear evidence that these cells are essential, dynamic participants in the regenerative process rather than passive bystanders.<\/p>\n The team also utilized the model to investigate the impact of aging on these regenerative capabilities. By cultivating cells from mice of different ages, the researchers identified a clear decline in the ability to produce new neurons as the organism aged. While the study suggests this reduction is likely linked to a decrease in the GBC population, the team emphasizes that further research is required to confirm this hypothesis. Should this mechanism be verified, it could provide a foundation for developing therapies aimed at rejuvenating these stem cell populations to restore olfactory function in aging populations.<\/p>\n A primary priority for the research team, led by former visiting Ph.D. student Juliana Gutschow Gameiro, was the development of a model that could be replicated by laboratories with limited resources. Gameiro, who came to Tufts from the State University of Londrina in Brazil, focused on designing a system that would remove the barriers of high costs and specialized equipment, allowing a broader community of scientists to investigate olfactory health.<\/p>\n The urgency of this work has been amplified by the global health landscape of the last several years. "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 The accessibility of this new model is a strategic move to democratize research into neuroregeneration. By creating a tool that non-stem cell biologists can easily adopt, the team hopes to accelerate the discovery process regarding why the olfactory system eventually fails in various disease states. "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," Lin adds.<\/p>\n The successful validation of the mouse-tissue organoid is viewed by the researchers as a significant stepping stone toward the ultimate goal: the creation of a human olfactory organoid. Such a model would serve as a vital platform for pre-clinical drug screening, allowing researchers to test potential treatments for anosmia in a controlled environment without the ethical and logistical complexities of using whole animal models or traditional human cell cultures.<\/p>\n The use of organoids has already revolutionized research in other areas of human biology, including the study of lung and kidney tissue. However, creating a similar model for the olfactory system presents unique challenges. Obtaining pure olfactory tissue from human subjects is a delicate procedure, often involving the collection of samples via a nasal brush\u2014similar to the swabs used in COVID-19 testing\u2014which reach deep into the nasal cavity. <\/p>\n The primary hurdle, according to Lin, lies in the complexity of the samples obtained. When scientists collect cells from the human nose, the sample contains a mixture of both respiratory stem cells and olfactory stem cells. Distinguishing between these two types in a laboratory setting has proven difficult, making it challenging to isolate the specific cells required to generate a high-quality organoid.<\/p>\n The research team is now shifting its focus to overcoming this obstacle. Their next objective is to develop a reliable, cost-effective technique that can separate human olfactory stem cells from the surrounding respiratory tissue and successfully coax them to proliferate in a laboratory environment. By bridging the gap between the established mouse model and a viable human organoid, the researchers hope to move closer to clinical solutions for the millions of people worldwide suffering from a diminished or absent sense of smell. As the team continues to refine their techniques, the potential for personalized, regenerative medicine for the olfactory system remains a promising frontier in modern biology.<\/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 new understanding of how the human nose maintains its sense of smell, identifying a previously underestimated stem cell population that plays a critical role in tissue repair. By engineering a novel, three-dimensional model to study the […]<\/p>\n","protected":false},"author":1,"featured_media":2777,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[650],"tags":[1823,4405,652,451,2485,656,4753,1166,666,3379,270,651],"class_list":["post-2778","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-health-and-wellness","tag-breakthrough","tag-dimensional","tag-fitness","tag-health","tag-hidden","tag-model","tag-olfactory","tag-regeneration","tag-reveals","tag-secrets","tag-three","tag-wellness"],"_links":{"self":[{"href":"https:\/\/xesi.net\/index.php?rest_route=\/wp\/v2\/posts\/2778","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=2778"}],"version-history":[{"count":0,"href":"https:\/\/xesi.net\/index.php?rest_route=\/wp\/v2\/posts\/2778\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/xesi.net\/index.php?rest_route=\/wp\/v2\/media\/2777"}],"wp:attachment":[{"href":"https:\/\/xesi.net\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=2778"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/xesi.net\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=2778"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/xesi.net\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=2778"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}Decoding the Cellular Communication Network<\/h3>\n
An Accessible Tool for Global Research<\/h3>\n
From Mouse Organoids to Human Therapeutics<\/h3>\n