BOSTON – Researchers at Tufts University School of Medicine and the Graduate School of Biomedical Sciences (GSBS) have discovered that a specific type of stem cell, previously thought to be dormant, plays a crucial role in preserving the sense of smell. This finding was made using a newly developed three-dimensional model that studies the regeneration of nerve tissue in the nose.

Sensory neurons in the nasal cavity possess a remarkable ability to regenerate throughout life, unlike cells in the central nervous system.This regeneration occurs despite constant exposure to the external surroundings.

Conditions such as viral infections like COVID-19, exposure to toxins, and aging can impair the function and replication of these cells, potentially leading to a partial or complete loss of smell. To better understand how neurons are continually formed in the nose and why this process declines with disease and age, the research team created an accessible three-dimensional olfactory tissue mouse model, known as an organoid.

The research, recently published in Cell Reports methods, utilizes this mouse model to demonstrate how two types of stem cells in the nose, horizontal basal cells (HBCs) and globose basal cells (GBCs), interact and support each other in the progress of new smell-sensing nerve tissue.

“Our research suggests that these two stem cells may be interdependent,” says Brian Lin, senior author on the study and a research assistant professor in the Department of Developmental, Molecular and chemical Biology. “One type that we thought was largely dormant — HBCs — may actually play a crucial role in supporting the production of new neurons and the repair of damaged tissue.”

The team identified a specific subpopulation of HBCs, characterized by their production of the protein KRT5, which actively supports the generation of new olfactory neurons.These HBCs were found to play a key role in the formation of organoids. Selectively removing these cells from the organoid cultures significantly impaired the generation of new neurons, indicating their essential role in the regenerative process.

“We also looked at cells from mice of different ages and grew them in the model,” Lin says. “We found a decline in the ability of the older mice cells to generate new neurons. We think this is due to a decrease in the GBC population as we age, but we need to do more work to test this hypothesis and if so, develop ways to rejuvenate them.”

Developing an Accessible Model

Juliana Gutschow gameiro, the lead author of the study and a former Ph.D. student visiting GSBS from the State University of londrina, Parana, in Brazil, focused on creating a model that could be easily replicated in labs with limited resources.

“As loss of smell is associated with COVID-19, as well as