Innovative 3D Model Sheds Light on How the Sense of Smell Regenerates
A newly developed three-dimensional tissue model is offering scientists unexpected insights into how the human sense of smell regenerates and why it frequently diminishes with age or illness. Published in the journal Cell Reports Methods, the research was conducted by a team at Tufts University School of Medicine and the Graduate School of Biomedical Sciences, alongside collaborating institutions. The breakthrough centers on the behavior of specific stem cells within the nasal cavity and could eventually pave the way for targeted therapies addressing smell loss.
Unlike cells found in the central nervous system, sensory neurons inside the nasal passage possess a remarkable capacity to regenerate throughout a person’s life, despite enduring continuous exposure to external environmental elements. However, viral infections like COVID-19, environmental toxins, and the natural aging process can impair this function, leading to partial or complete olfactory decline. To better observe how these sensory neurons form and why the regeneration cycle breaks down, the Tufts research team designed an accessible, affordable three-dimensional mouse olfactory tissue model, or organoid.
The investigation focused on two distinct classifications of stem cells residing within the nose: horizontal basal cells and globose basal cells. Prior scientific assumptions categorized horizontal basal cells as largely dormant. Yet, the team’s observations demonstrated that these populations actually interact closely to foster tissue repair. According to Brian Lin, senior author on the study and a research assistant professor in the Department of Developmental, Molecular and Chemical Biology at Tufts, the two stem cell types are interdependent, with the previously underestimated horizontal basal cells playing an essential role in producing new neurons and mending injured tissue.
Specifically, the researchers identified a subpopulation of horizontal basal cells defined by their production of the protein KRT5. When the investigators selectively depleted these specific cells from the organoid cultures, the creation of fresh neurons experienced significant impairment. Furthermore, when testing cells extracted from mice of varying ages, the team noted a clear reduction in the capacity of older tissue samples to generate new neurons, a phenomenon they attribute to a dwindling globose basal cell population over time.
Led by former visiting Ph.D. student Juliana Gutschow Gameiro, the study intentionally prioritized the creation of an inexpensive and easy-to-replicate system. Brian Lin emphasized that because conditions such as COVID-19 and Parkinson’s disease are frequently linked to olfactory dysfunction, researchers from diverse scientific backgrounds are increasingly studying the nasal epithelium. Providing a simplified laboratory model allows non-stem-cell specialists and laboratories with limited financial resources to investigate neurogenesis and identify the root causes of regenerative failure.
Looking ahead, the research group aims to transition this methodology toward human tissue. The ultimate objective is to establish a human olfactory organoid capable of screening potential pharmaceutical drugs for patients experiencing chronic smell loss. While human respiratory and olfactory stem cells are currently challenging to isolate cleanly from routine nasal swabs, the team is working on developing simple, cost-effective isolation techniques to bring human olfactory organoids into pre-clinical research.
Source: ScienceDaily Health & Medicine
