About 12% of Americans have lost their sense of smell due to head trauma, genetic defects or a natural decline of sensory neurons that occurs with age. A team of researchers at the University of Miami Miller School of Medicine is developing a potential remedy to this problem that consists of adult stem cells and may be able to be delivered in a simple nose drop.
The researchers developed a nose drop that contains globose basal cells (GBCs), which are replicating stem cells that restore damaged olfactory sensory neurons. When they tested the solution in mice that had been engineered to lose their sense of smell, the animals responded normally to bad odors. They published the findings in the journal Stem Cell Reports.
The team started by developing a mouse that’s unable to sense odors because it lacks cilia, the tiny hairs inside the nose that transmit signals to the brain. They created the model by deleting a gene called Ift88. When they delivered the stem cells to the Ift88-deficient mice, the cells created olfactory sensory neurons inside the linings of their noses, the researchers discovered.
The researchers compared the behavior of Ift88-deficient mice who received the stem cells to those that did not after both groups were exposed to bad odors. Only the animals that were treated pulled away from the noxious smells.
By studying the engrafted cells, the researchers were able to determine that the new neurons were sending axons to the olfactory “bulb” in the brain, which restored a sense of smell.
The olfactory epithelium, the thin layer of tissue inside the nose, contains GBCs and horizontal basal cells (HBCs), both of which are of interest to researchers who are searching for new methods for restoring the ability to smell. Researchers at Tufts University reported in March that they figured out how to culture HBCs and coax them to develop into olfactory epithelial cells—a feat that had eluded scientists in the past, because those cells generally stay dormant until they are activated by injuries.
The University of Miami researchers were pleasantly surprised to see that the GBCs they studied were able to engraft in the epithelium after being delivered via a nose drop. However, they warn that translating the therapy to people will be challenging.
"To be potentially useful in humans, the main hurdle would be to identify a source of cells capable of engrafting, differentiating into olfactory neurons, and properly connecting to the olfactory bulbs of the brain,” said senior author Bradley Goldstein, M.D., Ph.D., associate professor and otolaryngologist at the Miller School, in a statement.
Goldstein’s team is now planning further studies that will be designed to better understand the conditions that cause people to lose their sense of smell. They are also probing the mechanisms required for stem cells to transform into functioning olfactory neurons—knowledge that “will be broadly important for moving forward," Goldstein said.