Medical News Damaged sense of smell fixed in mice by squirting stem cells up nose

Medical News

Health

30 May 2019

Sense of smell restoredYuliya Duzhnikova / Alamy Stock Photo
By Ruby Prosser ScullyMice without a sense of smell have had the ability restored using stem cells delivered through the nose. The approach could pave the way for therapies that work in humans.
One in eight adults in the US has problems with olfaction as a consequence of ageing, infection, physical trauma or a genetic disorder. Most issues with smell are permanent, and there are few treatments, says Bradley Goldstein at the University of Miami.
While some studies have had success restoring smell in rodents using viral gene therapy, this is tailored for specific conditions. A stem cell-based approach could deal with a much broader set of olfactory problems.

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Goldstein says that many of the smell disorders that people develop through life appear to arise from problems in the tissue lining the nasal cavity, the olfactory epithelium.
“It seems like some failures might be in repairing damage,” Goldstein says. “So we were really interested to know if there was a way to replace or restore those damaged cells that could be beneficial.”

First, they genetically modified mice so that the neurons in their noses that are needed to sense smells – olfactory sensory neurons – didn’t have any of the hair-like structures that normally pick up odours.
Then Goldstein and his team squirted droplets of so-called basal cells, which are responsible for the replacement of these neurons when they are old or damaged, into the rodents’ noses.
These stem cells successfully created mature, working olfactory sensory neurons in the nasal cavity, which then connected to the olfactory bulb in the brain.
When they tested the mice, they found those that were genetically modified with the faulty smelling neurons showed an inability to detect a bad smell. However, those with the genetic modification that had then had the stem cell treatment reacted to the smell in the way a regular mouse would.
As well as the simple joy that comes from smelling a rose or the flood of memories sparked by sniffing a lover’s jumper, our sense of smell is a vital and effective warning system. Smoke, chemicals and spoiled food are all dangers that we can avoid with a healthy sense of smell, Goldstein says.
While Goldstein and his team found no evidence that mice developed tumours from the therapy, he notes that there are many more safety and efficacy hurdles to pass before the technique could be tested in humans.
“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,” Goldstein says.
Journal reference: Stem Cell Reports, DOI: 10.1016/j.stemcr.2019.05.001

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