New 3D Model Uncovers Nose’s Regenerative Secrets

Scientists have created a 3D model of mouse tissue to observe how the nose recovers smell-sensing neurons. The objective is to develop a system to test treatments for the loss of smell, a problem that impacts many.

Unexpected Discovery

Research from Tufts University School of Medicine and the Graduate School of Biomedical Sciences (GSBS), using a new 3D model, has uncovered an unexpected element in our sense of smell. Their findings highlight how a type of stem cell, once thought to be mostly inactive, supports the regeneration of olfactory neurons.

“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.”

—Brian Lin

Around 5% of the world’s population experiences smell disorders (National Institutes of Health, 2020).

How Regeneration Works

Sensory neurons in the nasal cavity can regenerate. This resilience is regularly tested by exposure to environmental factors, viral infections, and aging. These elements can impact function and cell replication, leading to a partial or complete loss of smell.

To better understand how olfactory neurons regenerate, researchers at Tufts developed a 3D olfactory tissue model derived from mouse cells. This model enables scientists to research how new sensory neurons form in the nose and why this process declines with age or disease.

Stem Cell Collaboration

The study, published in Cell Reports Methods, centers on horizontal basal cells (HBCs) and globose basal cells (GBCs), two types of olfactory stem cells. Researchers discovered these cells actively participate in neuroregeneration and work in close communication to produce new smell-sensing tissue.

Role of KRT5

The scientists found a subpopulation of HBCs defined by the production of the protein KRT5. These KRT5-positive HBCs actively support the generation of new olfactory neurons within the model.

Impact of Aging

Researchers also explored aging’s effect on the regenerative process. They discovered that older mice cells had a decreased ability to generate new neurons. The team speculates this is due to a reduction in the GBC population as we age. However, more research is needed.

Toward Human Organoids

The project’s main goal is to translate the mouse tissue model into a human organoid system. This system will screen potential therapies for individuals with a lost sense of smell.

The challenge is to develop an affordable, reliable way to isolate human olfactory stem cells and encourage them to grow in culture. This will help bring smell-restoring therapies closer to reality.