Researchers at the University of Miami Miller School of Medicine have developed stem cell nose drops that has restored the sense of smell in mice.
When olfactory sensory neurons are damaged or become old, globose basal cells (GBCs) come to the rescue. GBCs are replicating stem cells that restore olfactory sensory neurons when they are damaged. The researchers conducted a study to determine whether droplets of GBCs sprayed into the nose restore the function of olfactory sensory neurons.
In order to test their nose drops, the researchers developed a novel mouse model with inducible hyposmia. The mice had olfactory sensory neurons, but they lacked the cilia that are required to detect odors. This was achieved by deleting the gene Ift88.
After treatment with the nose drops, the mice lacking the Ift88 gene responded when exposed to noxious smells, whereas the mice in the control group did not. The researchers discovered the GBCs had developed into fully functional, mature olfactory sensory neurons in the lining of the nose, which stretched through to the olfactory bulb in the brain.
“The olfactory nerves are kind of the highway that connect up through the roof of the nose intracranially to connect to the brain, so we certainly want to make sure that there’s no unintended delivery of cells to other places where we didn’t want them to go,” said Bradley Goldstein M.D., Ph.D., associate professor and otolaryngologist at Miller School of Medicine. The researchers found no evidence of tumor formation in the mice following treatment and there appeared to be no ill effects.
Approximately 12% of the population of the United States has impaired olfaction to some degree. When the sense of smell is lost, there are no treatment options available. Some studies have been conducted using viral gene therapy which have restored the sense of smell in rodents, although the potential uses of that technique are limited to specific conditions. A stem cell approach has greater potential for treating a broader range of olfactory problems.
However, developing a stem-cell based treatment has been problematic as it is difficult to isolate and activate GBCs. The olfactory epithelium contains GBCs which are usually activated following an injury, but otherwise remain dormant. “We were a bit surprised to find that cells could engraft fairly robustly with a simple nose drop delivery,” explained Goldstein.
While the study has produced exciting results, there are several challenges to overcome before the treatment could be used in humans. It would be necessary to find a suitable source of cells that are capable of engrafting and differentiating into olfactory neurons that can connect to the olfactory bulb in the brain, extensive tests would be required to ensure the treatment is safe, and it would also be necessary to determine when such a therapy would be appropriate.
Further studies have now been planned to define specific problems that cause olfactory impairment in humans and the mechanisms in human cells that are necessary for the development of functional, mature, olfactory sensory neurons. It will then be possible to determine what the best form of treatment will be: A stem cell-based treatment, viral gene therapy, or other pharmacologic targets.
The study – Cell-Based Therapy Restores Olfactory Function in an Inducible Model of Hyposmia – was recently published in the journal Stem Cell Reports. DOI: 10.1016/j.stemcr.2019.05.001