Olfaction is impaired in 12% of the US population due to causes such as age-related decline, post-viral damage, head trauma, or genetic disorders affecting olfactory neuron function. Impairments in the sense of smell are often permanent and lack treatment options. Recent studies in mice have shown the potential of viral gene therapy to restore olfactory function. But viral gene therapies are usually tailored only to specific conditions. By contrast, cellular replacement therapy holds promise for recovering olfactory function that is impaired due to a wide range of causes.
To test this idea, Goldstein and his team developed a genetic mouse model that cannot detect odors due to non-functional olfactory sensory neurons. Specifically, deletion of the Ift88 gene caused these cells to lack cilia — hair-like structures that are required for sensing odors. The researchers then delivered into the nose droplets containing globose basal cells — the principal pool of replicating stem cells that replenish aging or damaged olfactory sensory neurons throughout life.
The adult stem cells engrafted to produce mature, functional olfactory sensory neurons in the olfactory epithelium, tissue inside the nasal cavity. The engraftment-derived olfactory sensory neurons sent projections, or axons, to a brain structure called the olfactory bulb, effectively restoring the sense of smell. In a behavioral test, Ift88-deficient mice that received the stem cell therapy responded normally to an aversive odor, while Ift88-deficient mice that didn’t receive the stem cell therapy did not. Moreover, there was no evidence of tumor growth within the timeframe of the study, supporting the potential safety of this treatment.
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.
Sarah Kurtenbach, Garrett M. Goss, Stefania Goncalves, Rhea Choi, Joshua M. Hare, Nirupa Chaudhari, Bradley J. Goldstein. Cell-Based Therapy Restores Olfactory Function in an Inducible Model of Hyposmia. Stem Cell Reports.Retrieved from : https://www.cell.com/stem-cell-reports/fulltext/S2213-6711(19)30146-8?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2213671119301468%3Fshowall%3Dtrue
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