Nose drop with globose basal cells enabled mice to respond normally to odors.
Loss of the sense of smell is not uncommon. It can occur naturally as part of the aging process, due to head trauma or as the result of genetic defects. The sense of smell is dependent on a number of factors, including the presence of cilia, tiny hairs inside the nose that transmit signals to the brain, and globose basal cells (GBCs) and horizontal basal cells (HBCs) in the olfactory epithelium, the thin layer of tissue inside the nose.
Much research has focused on GBCs and HBCs. GBCs are replicating stem cells that restore damaged olfactory sensory neurons. Recently, researchers at Tufts University cultured HBCs, which normally remain dormant until activated by injury, that develop into olfactory epithelial cells. Now scientists at the University of Miami Miller School of Medicine have developed adult stem cells formulated as a nose drop that may help restore the sense of smell.
The nose drops contain GBCs. The researchers delivered them to specially engineered mice with deletions of the Ift88 gene, which is required for formation of cilia in olfactory sensory neurons. In cilia-deficient mice treated with the GBC-containing nose drops, new olfactory sensory neurons with functional cilia were created inside the linings of their noses. These newly created neurons sent axons to the olfactory “bulb” in the brain, restoring the sense of smell. As a result, the mice responded normally when exposed to bad odors. Mice that were not treated with the stem cells did not pull away from the noxious odors.
These results are promising, but much work is yet to be done before they can be translated into a treatment for humans. The first big step is to identify a source of cells capable of engrafting, differentiating into olfactory neurons and properly connecting to the olfactory bulbs of the brain, according to lead researchers Bradley Goldstein, M.D., Ph.D., associate professor and otolaryngologist at the Miller School.
The group is planning further studies to better understand the conditions that lead to loss of smell and to determine the mechanisms involved in the transformation of stem cells into functioning olfactory neurons, making it possible to identify potential source cells for a human therapy.