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 identified a critical, previously overlooked function of stem cells within the nose. By utilizing a newly devised, three-dimensional model to study the regeneration of nerve tissue, the research team discovered that a specific population of stem cells, once widely believed to be largely dormant, actually plays a vital role in maintaining the sense of smell.<\/p>\n
Unlike the central nervous system, where damage is often permanent, the sensory neurons within the nasal cavity possess a remarkable capacity for self-renewal. Throughout a person\u2019s life, these neurons regenerate, a process that is essential given the nasal cavity’s constant exposure to environmental pathogens, toxins, and pollutants. However, this regenerative ability is not invincible. Viral infections\u2014most notably those caused by COVID-19\u2014as well as long-term exposure to toxins and the natural processes of aging can compromise these cells. When the delicate machinery of neuronal replication falters, individuals often suffer from a partial or total loss of smell, a condition that can have profound impacts on nutrition, safety, and overall quality of life.<\/p>\n
To better investigate the mechanics behind this decline, the Tufts research team developed an innovative, three-dimensional olfactory tissue mouse model, or organoid. This "mini-organ" allows scientists to observe, in real-time, how neurons are continually formed in the nose and to pinpoint the precise biological bottlenecks that occur during disease or aging. The study, which was recently published in the journal Cell Reports Methods<\/em>, provides a granular look at the symbiotic relationship between two distinct types of stem cells: horizontal basal cells (HBCs) and globose basal cells (GBCs).<\/p>\n The findings challenge long-held assumptions about cellular behavior. According to Brian Lin, a research assistant professor in the Department of Developmental, Molecular and Chemical Biology and the study\u2019s senior author, the team\u2019s research suggests a sophisticated level of interdependence between these two stem cell populations. "Our research suggests that these two stem cells may be interdependent," Lin explains. "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 leveraging their new 3D organoid model, the team identified a specific subpopulation of HBCs, distinguished by their production of the protein KRT5. These KRT5-positive cells were observed actively facilitating the generation of new olfactory neurons. To confirm their necessity, the researchers selectively depleted these cells from the organoid cultures. The result was a significant impairment in the generation of new neurons, underscoring that these cells are far from dormant; rather, they are essential, active participants in the regenerative architecture of the olfactory system.<\/p>\n The research also delved into the impact of age on these regenerative processes. By growing cells from mice of varying ages within the organoid model, the team observed a clear decline in the ability of older cells to generate new neurons. Lin and his colleagues hypothesize that this decline is rooted in a reduction of the GBC population over time. While the team plans to conduct further studies to validate this hypothesis, the finding offers a potential roadmap for future therapeutic interventions. If the loss of GBCs is indeed the primary driver of age-related olfactory decline, the next phase of research will focus on developing strategies to rejuvenate these cells or stimulate their proliferation.<\/p>\n A primary driver behind the success of this study was the intentional design of the organoid model. The lead author of the study, Juliana Gutschow Gameiro, a former Ph.D. student visiting GSBS from the State University of Londrina in Brazil, worked extensively to ensure the model was accessible. Her goal was to create a tool that could be easily replicated in laboratories that might not have the extensive funding or specialized equipment available at top-tier research institutions.<\/p>\n This accessibility is particularly timely. The global health crisis triggered by COVID-19 brought the issue of olfactory loss into the mainstream, with millions of people reporting a diminished sense of smell as a symptom of the infection. Furthermore, olfactory dysfunction is a recognized early clinical indicator for neurodegenerative conditions such as Parkinson’s disease. Consequently, the last few years have seen a surge in interest among researchers from diverse scientific disciplines who are eager to study olfactory epithelial cells.<\/p>\n "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 says. By lowering the barrier to entry for this type of research, the team hopes to foster a collaborative environment where scientists worldwide can contribute to solving the mystery of why our sense of smell fades.<\/p>\n The ultimate objective of the Tufts team is to translate their success with mouse-tissue models into a functional human organoid. Such a model would serve as a high-throughput platform for drug screening, allowing researchers to test therapeutic compounds in a controlled environment to see if they can reverse or treat olfactory loss in patients.<\/p>\n The transition from mouse to human models offers significant advantages over current methods. Organoids can make pre-clinical research both faster and more cost-effective, while simultaneously reducing the reliance on whole-animal testing. While organoids have already been successfully developed for other organs, including the lungs and kidneys, human olfactory tissue remains a significant challenge.<\/p>\n The primary hurdle lies in the collection and isolation of the tissue. Currently, to obtain olfactory tissue from a human patient, clinicians must perform a procedure involving a brush\u2014similar to those used for COVID-19 testing\u2014which is inserted deep into the nasal cavity under anesthesia. The problem, according to Lin, is that the collected samples are a complex mixture of respiratory stem cells and olfactory stem cells. Unlike the mouse model, where these cell types are easier to distinguish and separate, human samples are currently difficult to purify.<\/p>\n The research team\u2019s next major challenge is to develop a reliable, inexpensive, and technically simple method to isolate these human olfactory stem cells and cultivate them in the lab. Once this technique is perfected, the ability to create patient-specific olfactory organoids could revolutionize the way we treat sensory loss. By screening drugs against a patient’s own tissue in an organoid, clinicians could move toward a more personalized approach to restoring the sense of smell.<\/p>\n As the team continues to refine their methodology, the focus remains on bridging the gap between basic cellular biology and clinical application. By uncovering the hidden roles of "dormant" stem cells and democratizing the tools used to study them, the researchers at Tufts are laying a vital foundation for future breakthroughs in regenerative medicine. Whether through drug discovery or cellular rejuvenation, the prospect of restoring a sense of smell for those who have lost it is becoming an increasingly tangible reality.<\/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 identified a critical, previously overlooked function of stem cells within the nose. By utilizing a newly devised, three-dimensional model to study the […]<\/p>\n","protected":false},"author":1,"featured_media":3636,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[650],"tags":[2672,4385,652,451,2485,4450,653,1647,658,659,2671,1160,651],"class_list":["post-3637","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-preserving","tag-researchers","tag-role","tag-sense","tag-smell","tag-stem","tag-uncover","tag-wellness"],"_links":{"self":[{"href":"https:\/\/xesi.net\/index.php?rest_route=\/wp\/v2\/posts\/3637","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=3637"}],"version-history":[{"count":0,"href":"https:\/\/xesi.net\/index.php?rest_route=\/wp\/v2\/posts\/3637\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/xesi.net\/index.php?rest_route=\/wp\/v2\/media\/3636"}],"wp:attachment":[{"href":"https:\/\/xesi.net\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=3637"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/xesi.net\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=3637"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/xesi.net\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=3637"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}An Easy-To-Use Model for Global Research<\/h2>\n
Paving the Way for Human Organoids<\/h2>\n