3D Nose Model Reveals Unexpected Players In Sense Of Smell Regeneration

In a significant advancement for sensory science, researchers at Tufts University School of Medicine and the Graduate School of Biomedical Sciences (GSBS) have developed a new three-dimensional model to investigate how nerve tissue in the nose regenerates.

Their findings, published in Cell Reports Methods, suggest that a type of nasal stem cell, once believed to be largely dormant, is in fact essential in restoring the sense of smell.

Unlike cells in the central nervous system, olfactory sensory neurons have the remarkable ability to regenerate throughout life.

However, this regenerative process can be compromised by viral infections such as COVID-19, exposure to environmental toxins, or the natural effects of ageing, leading to partial or total loss of smell.

A simple, effective 3D mouse tissue model

To better understand the mechanisms behind this regeneration, the research team created a simple yet effective 3D mouse-tissue model, also referred to as an ‘organoid’.

Scientists use this model to observe how the nose forms new smell-sensing neurons and to understand why this process may decline over time or during disease.

The study focuses on two types of stem cells found in the nasal lining, horizontal basal cells (HBCs) and globose basal cells (GBCs).

Senior author Dr Brian Lin, a research assistant professor in the Department of Developmental, Molecular and Chemical Biology, explained, “Our research suggests that these two stem cells may be interdependent.”

Dormant stem cells found active

In particular, the team identified a subpopulation of HBCs that express a protein known as KRT5.

Researchers once thought these cells were inactive, but they found that the cells actively support the development of new olfactory neurons.

When researchers removed these HBCs from the organoid cultures, neuron generation dropped significantly, showing their essential role in tissue repair.

Moreover, researchers observed a decline in the regenerative capacity of stem cells taken from older mice.

The researchers primarily attributed this decline to a reduction in the GBC population, highlighting the need for further study into age-related sensory loss.

Dr Lin emphasised that the team designed this model so that laboratories with limited funding can easily replicate it, making it an accessible tool for future research.

The team aims to adapt this model in the long term to create a human olfactory organoid that can screen drugs and develop treatments for individuals suffering from smell disorders.

This pioneering research paves the way for a better understanding, prevention, and potentially reversal of smell loss, bringing new hope to those affected by age, illness, or injury.

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