In a significant breakthrough for sensory biology, a team of researchers at the Tufts University School of Medicine and the Graduate School of Biomedical Sciences (GSBS) has identified that a specific type of stem cell, previously thought to be largely dormant, plays a critical and active role in preserving the human sense of smell. By developing a novel, three-dimensional model to study the regeneration of nasal nerve tissue, the scientists have uncovered a complex, interdependent relationship between different stem cell populations, offering new hope for addressing olfactory loss caused by disease, aging, or environmental factors.<\/p>\n
The human sense of smell is remarkably resilient, yet it is also surprisingly vulnerable. Unlike the neurons in the central nervous system, which are notoriously difficult to repair or replace, the sensory neurons housed within the nasal cavity possess a unique capacity for regeneration throughout an individual\u2019s entire lifespan. This is an essential evolutionary adaptation, as these cells are in constant, direct contact with the external environment\u2014and therefore, the various pathogens, pollutants, and irritants that enter the nose with every breath.<\/p>\n
However, this regenerative capacity is not infinite. Viral infections\u2014most notably SARS-CoV-2\u2014as well as prolonged exposure to environmental toxins and the natural process of biological aging, can impair the function of these neurons. In many cases, the body\u2019s ability to replicate these essential cells falters, leading to a diminished sense of smell or, in some instances, complete anosmia. Until now, the precise mechanisms governing how these neurons are continually formed, and why that process eventually declines, have remained somewhat elusive.<\/p>\n
To investigate these phenomena, the Tufts research team, led by senior author Brian Lin, a research assistant professor in the Department of Developmental, Molecular and Chemical Biology, developed a new three-dimensional olfactory tissue mouse model, or organoid. The findings from this research, which were recently published in the journal Cell Reports Methods<\/em>, provide a detailed look at how two distinct types of stem cells in the nose\u2014horizontal basal cells (HBCs) and globose basal cells (GBCs)\u2014interact to generate new smell-sensing nerve tissue.<\/p>\n For years, the scientific consensus categorized HBCs as a relatively quiet, dormant population of cells, often sidelined in favor of the more active GBCs. However, the new organoid model has challenged this long-held assumption. According to Dr. Lin, the research indicates that these two stem cell types may be fundamentally interdependent, functioning as a collaborative unit rather than independent actors.<\/p>\n "Our research suggests that these two stem cells may be interdependent," Dr. Lin explained. "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 model, the team identified a specific subpopulation of HBCs, which are distinguished by their production of the protein KRT5. The researchers observed that these particular cells are essential for the structural and functional formation of the organoids themselves. Perhaps most telling was the experiment in which these KRT5-producing HBCs were selectively depleted from the cultures. The result was a significant impairment in the generation of new olfactory neurons, confirming that these cells are not merely bystanders, but are, in fact, essential players in the regenerative cycle of the nose.<\/p>\n The team also examined how this regenerative capacity shifts over time. By comparing cells taken from mice of different ages, the researchers observed a clear decline in the ability of older cells to generate new neurons. While further investigation is required to confirm the exact mechanisms, the team suspects that this decline is linked to a reduction in the GBC population. If this hypothesis holds, it could provide a roadmap for developing future therapies aimed at "rejuvenating" these cells to restore lost olfactory function in aging populations.<\/p>\n A primary objective of the study was to ensure that the research methodology would be accessible to a wide range of laboratories, even those operating with limited resources. Juliana Gutschow Gameiro, the lead author of the study and a former Ph.D. student visiting GSBS from the State University of Londrina in Brazil, spearheaded the development of this model with a focus on ease of use and affordability.<\/p>\n The urgency for such a tool has increased dramatically in recent years. As the COVID-19 pandemic brought the prevalence and impact of olfactory loss into the global spotlight, a surge of interest from researchers across diverse fields\u2014including those studying Parkinson\u2019s disease and other neurodegenerative conditions where loss of smell is a frequent early indicator\u2014has turned toward the biology of the olfactory epithelium.<\/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," Dr. Lin noted. "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 successful deployment of the mouse-tissue model is viewed by the researchers as a vital stepping stone toward the ultimate goal: the creation of a human organoid. Such a model would serve as a powerful platform for pre-clinical drug screening, allowing scientists to test potential therapies for patients whose sense of smell has been significantly compromised or lost entirely.<\/p>\n Organoids represent a significant leap forward in medical research. By providing a three-dimensional environment that mimics the complexity of human tissue, they offer a faster, more cost-effective, and potentially more accurate alternative to traditional methods, such as whole-animal testing or standard two-dimensional cell cultures. While organoids have already been successfully developed for other organs, including the lungs and kidneys, the development of a human olfactory organoid remains a complex challenge.<\/p>\n The primary hurdle lies in the collection and purification of the tissue. Obtaining pure olfactory tissue from human subjects is a difficult procedure, typically involving the use of a brush-like device inserted deep into the nasal cavity under anesthesia. Unlike the mouse model, the human samples collected via this method are often a heterogeneous mixture of respiratory stem cells and olfactory stem cells, which are notoriously difficult to separate.<\/p>\n As the team looks to the future, their focus has shifted toward solving this technical puzzle. The next phase of their work involves perfecting a simple, cost-effective technique that can reliably isolate human olfactory stem cells and provide the necessary conditions for them to thrive and regenerate in a laboratory setting. By bridging the gap between mouse models and human tissue, the researchers at Tufts hope to pave the way for a new era of restorative medicine for the olfactory system, offering a path to recovery for the millions of people worldwide who live with the profound impact of diminished sensory function.<\/p>\n","protected":false},"excerpt":{"rendered":" In a significant breakthrough for sensory biology, a team of researchers at the Tufts University School of Medicine and the Graduate School of Biomedical Sciences (GSBS) has identified that a specific type of stem cell, previously thought to be largely dormant, plays a critical and active role in preserving the human sense of smell. By […]<\/p>\n","protected":false},"author":1,"featured_media":2531,"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-2532","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\/2532","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=2532"}],"version-history":[{"count":0,"href":"https:\/\/xesi.net\/index.php?rest_route=\/wp\/v2\/posts\/2532\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/xesi.net\/index.php?rest_route=\/wp\/v2\/media\/2531"}],"wp:attachment":[{"href":"https:\/\/xesi.net\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=2532"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/xesi.net\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=2532"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/xesi.net\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=2532"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}Unmasking the Role of Horizontal Basal Cells<\/h3>\n
A Accessible Model for Global Research<\/h3>\n
Moving Toward Human Organoids<\/h3>\n