The sudden influx of interest in olfaction following the pandemic meant that scientists who were not traditionally stem cell biologists were suddenly tasked with understanding nasal tissue. The Tufts model serves as a bridge for these researchers.
"We wanted to develop an easy-to-use model so that non-stem cell biologists and those working in labs with limited resources could use it to better understand how olfactory neurons regenerate and what happens that causes that process to diminish or fail completely," Lin says.
Next Step: A Human Organoid
While the mouse-tissue model has provided invaluable insights into the interplay between HBCs and GBCs, the ultimate objective for the Tufts team is to translate these findings into human health applications. The mouse organoid serves as a critical proof-of-concept and a pathway toward the development of a human olfactory organoid.
The creation of a human version of this model would be a transformative step for the pharmaceutical industry. Currently, drug discovery for conditions affecting the sense of smell is a slow and costly process, often relying on animal testing or flat, two-dimensional cell cultures that do not accurately mimic the complexity of human biology. A 3D human organoid would allow for rapid, cost-effective screening of drugs to treat patients whose sense of smell has been damaged by illness or injury.
However, moving from mice to humans presents significant technical hurdles. "It’s challenging to get pure olfactory tissue from humans," Lin notes.
The current method for collecting these cells involves anesthetizing a patient and using a specialized brush—similar to the long swabs used in COVID-19 testing—to reach deep into the upper reaches of the nasal cavity. The primary difficulty is that this collection process often results in a mixture of different cell types. Unlike the mouse model, where researchers can more easily isolate specific stem cells, human samples frequently contain a blend of respiratory stem cells and olfactory stem cells that are notoriously difficult to separate.
The research team’s next major challenge is to refine a simple and inexpensive technique to isolate these human olfactory stem cells. Once they can reliably separate the "smell-sensing" stem cells from the "breathing" stem cells, they can begin coaxing them to grow into the 3D organoids needed for clinical research.
By uncovering the hidden activity of horizontal basal cells and providing a democratized tool for study, the researchers at Tufts have opened a new chapter in sensory science. Their work suggests that the "dormant" parts of our biology may hold the key to restoration, offering hope for those living in a world without scent.
