Spraying Stem Cells Up The Noses of Mice Has Restored Their Sense of Smell

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Imagine a simple and effective treatment for restoring the sense of smell in people who have lost it or never had it in the first place – that could one day be possible as a result of early stage research on mice, in which olfactory nerves were replenished using stem cells.

Using droplets of globose basal cells – the same cells that naturally replace damaged and ageing neurons related to smell – scientists were able to get them to develop into full nerve cells, stretching right into the brain.

Ultimately a few squirts of stem cells were able to reconnect the axons leading to the olfactory signalling in the brains of the mice. Scientists are still a long way from repeating the trick with human beings, but it’s a very promising start.

“This is the first model of smell loss showing evidence of recovery using a cell-based therapy,” says lead researcher and otolaryngologist Bradley Goldstein, from the University of Miami.

“It is very important to understand that many questions would need to be worked out before considering this in a human patient. However, it does provide evidence that such an approach warrants further study.”

Goldstein and his colleagues worked with mice that had been genetically modified to lose their sense of smell – in particular, the absence of the IFT88 gene meant the mice cells lacked cilia, the tiny hair-like structures that detect scents and odours.

After the globose basal cells were applied, and developed into fully mature olfactory sensory neurons inside the olfactory epithelium (the nasal cavity), the treated mice started reacting to bad smells.

“There is some evidence that a failure to normally replace damaged or lost olfactory neurons may contribute to many forms of acquired olfactory loss,” says Goldstein. “So, we were interested in testing the idea that a cell-based therapy approach, to replace neurons, might be plausible.”

“We were a bit surprised to find that cells could engraft fairly robustly with a simple nose drop delivery.”

In the US, 12 percent of the population have problems with their sense of smell, due to ageing, a genetic disorder, or some kind of injury. That’s almost 40 million people, and right now there aren’t a lot of treatments available.

With many of those issues seemingly linked to the olfactory epithelium and its tissue lining, this stem cell approach might work – though adapting the approach to see if it is as effective in human beings is going to take time. Scientists will also need to make sure there aren’t any adverse side effects.

A healthy sense of smell not only enriches life – when walking through a garden or a kitchen perhaps – it can also act as a useful warning system for everything from out-of-date food to a gas leak.

“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,” says Goldstein.

“Further, one would need to define what clinical situations might be appropriate, rather than the animal model of acute olfactory injury.”

The research has been published in Stem Cell Reports.