Summary: Researchers have developed a three-dimensional mouse organoid model aimed at examining the regeneration of neurons in the nose. This study indicates that a previously considered dormant type of stem cell might be key in repairing olfactory tissue. Specifically, horizontal basal cells (HBCs), distinguished by KRT5, actively facilitate neuron generation, working alongside globose basal cells (GBCs).
This model sheds light on how aging or viral infections, like COVID-19, can disrupt the functioning of these stem cells, ultimately affecting the sense of smell. The system is user-friendly and designed to be accessible for laboratories with limited resources, which may help in creating future human organoids for testing therapies aimed at smell loss.
Key Facts:
- Hidden Helpers: HBCs, once deemed inactive, play a crucial role in the regeneration of olfactory neurons.
- Aging Impact: Older mouse cells showed diminished ability to generate neurons, likely due to a decline in GBCs.
- Practical Tool: This model is low-cost and adaptable, making it suitable for widespread research on smell disorders.
Source: Tufts University
An innovative three-dimensional model to explore nerve tissue regeneration in the nose has emerged from researchers at Tufts University School of Medicine and the Graduate School of Biomedical Sciences (GSBS). They discovered that a type of stem cell, once thought inactive, may hold more importance in maintaining the sense of smell than expected.
Compared to the central nervous system, sensory neurons in the nasal cavity exhibit an impressive capacity to regenerate throughout an individual’s life, despite regular exposure to environmental factors.
However, things like viral infections, toxins, or simply aging can impair their functionality or their ability to replicate. This might lead to a partial or total loss of the sense of smell.
The research team established a straightforward, three-dimensional olfactory tissue mouse model, or organoid, aiming to provide insights into how neurons are continuously formed in the nose and the reasons behind any decline in this process due to disease and aging.
Their findings, published in Cell Reports Methods, demonstrate how two types of stem cells in the nose—horizontal basal cells (HBCs) and globose basal cells (GBCs)—interact and support one another in generating new olfactory nerve tissue.
“Our research indicates that these two stem cells might depend on each other,” explains Brian Lin, the study’s senior author and a research assistant professor in the Department of Developmental, Molecular, and Chemical Biology.
“The HBCs, which we thought were largely dormant, could actually be vital in fostering the production of new neurons and repairing damaged tissue.”
Using the model, the team located a specific group of HBCs, identifiable by their production of the protein KRT5, that significantly aids in generating new olfactory neurons.
The researchers noted that these specific HBCs are key in forming the organoids, and when they were selectively removed from the cultures, the formation of new neurons dropped sharply.
This evidence suggests that these previously dormant stem cells are crucial in the regenerative process.
Additionally, the team assessed cells from mice of varying ages in their model.
“We observed that the capability of cells from older mice to produce new neurons was diminished,” Lin notes. “This appears related to a decrease in the GBC population as we age, but more research is needed to explore this further and possibly find ways to rejuvenate them.”
An Accessible Model
Juliana Gutschow Gameiro, the lead author of the study and a former Ph.D. student who visited GSBS from Brazil, focused on creating a model that could be easily implemented in labs with limited funds and resources.
“Since loss of smell is linked to COVID-19, Parkinson’s disease, and other conditions, numerous researchers from diverse fields have become interested in studying olfactory epithelial cells lately,” Lin explains.
“Our aim was to create a straightforward model that not only stem cell biologists but also those in labs with fewer resources could utilize for a better understanding of olfactory neuron regeneration and the factors causing that process to reduce or fail altogether,” he adds.
Next Step: A Human Organoid
The ultimate aspiration is to leverage this mouse-tissue model of olfactory sensory neurons to develop a human organoid that could be employed in drug screening for individuals experiencing significant smell loss.
Organoids could make pre-clinical research faster, more cost-effective, and potentially more efficient compared to traditional animal testing or existing human cell cultures. While organoids have successfully been created for various organs, human olfactory tissue models remain undeveloped.
“It’s not easy to extract pure olfactory tissue from humans,” Lin notes.
The process involves anesthesia and using a brush similar to a COVID test swab deep within the nasal cavity. Unlike the mouse model, separating the human respiratory and olfactory stem cells obtained this way poses a challenge.
The research team’s next hurdle is to establish a straightforward, low-cost method for isolating human olfactory stem cells and encouraging their growth in laboratory settings.
Funding: This work was supported by the National Institutes of Health, the Coordenação de Aperfeiҫoamento de Pessoal de Nível Superior in Brazil, and the German Research Foundation under the Walter Benjamin Program, along with the Fritz Thyssen Foundation.
The findings reflect the authors’ views and may not necessarily represent the official stance of the funders.
