A Surprisingly Simple Stem Cell Therapy Restores Sense of Smell in Mice
The stem cell therapy noted here is close to the original, hoped-for vision for the field, in which transplanted cells survive and integrate with patient tissue in order to carry out useful work, restoring lost cells and tissue structure to improve function. That, as it turned out, is very hard to achieve. Typically, transplanted cells near all die, and the benefits produced by presently available stem cell therapies, such as reduced chronic inflammation, are instead mediated by signals secreted by the stem cells in the short time that they survive. Nonetheless, cell therapies in which large fractions of the transplanted cells survive to restore function remain an important goal in the field, and results such as those reported here help to keep that original vision alive.
In mice whose sense of smell has been disabled, a squirt of stem cells into the nose can restore olfaction, researchers report. The introduced globose basal cells, which are precursors to smell-sensing neurons, engrafted in the nose, matured into nerve cells, and sent axons to the mice's olfactory bulbs in the brain. "We were a bit surprised to find that cells could engraft fairly robustly with a simple nose drop delivery. 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. Further, one would need to define what clinical situations might be appropriate, rather than the animal model of acute olfactory injury."
Researchers have tried stem cell therapies to restore olfaction in animals previously, but it's been difficult to determine whether the regained function came from the transplant or from endogenous repair stimulated by the experimental injury to induce a loss of olfaction. So the team developed a mouse whose resident globose basal cells only made nonfunctional neurons, and any restoration of smell would be attributed to the introduced cells.
The team developed the stem cell transplant by engineering mice that produce easily traceable green fluorescent cells. The researchers then harvested glowing green globose basal cells (as identified by the presence of a receptor called c-kit) and delivered them into the noses of the genetically engineered, smell-impaired mice. Four weeks later, the team observed the green cells in the nasal epithelium, with axons working their way into the olfactory bulb. Behaviorally, the mice appeared to have a functioning sense of smell after the stem cell treatment. Unlike untreated animals, they avoided an area of an enclosure that had a bad smell to normal mice.