Posts Tagged ‘olfaction’

by KERRY GRENS

In mice whose sense of smell has been disabled, a squirt of stem cells into the nose can restore olfaction, researchers report today (May 30) in Stem Cell Reports. 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,” senior author Bradley Goldstein of the University of Miami Miller School of Medicine says in a press release. “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.”

Goldstein and others have independently tried stem cell therapies to restore olfaction in animals previously, but he and his coauthors note in their study that 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 his 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.

To move this technology into humans suffering from a loss of olfaction, more experiments in animals are necessary, says James Schwob, an olfactory researcher at Tufts University who has collaborated with Goldstein but was not involved in the latest study, in an interview with Gizmodo. “The challenge is going to be trying to [engraft analogous cells] in humans in a way . . . that [would] not make things worse.”

https://www.the-scientist.com/news-opinion/stem-cells-delivered-to-the-nose-restore-mices-ability-to-smell-65953

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An image depicting the measurement of nasal airflow while a child is presented with pleasant and unpleasant odors. Throughout the 10-minute study the children were seated comfortably in front of a computer monitor while viewing a cartoon. The nasal airflow measurement and the presentation of odorants were done using a modified pediatric nasal cannula and a custom built olfactometer.

Imagine the way you might smell a rose. You’d take a nice big sniff to breathe in the sweet but subtle floral scent. Upon walking into a public restroom, you’d likely do just the opposite–abruptly limiting the flow of air through your nose. Now, researchers reporting in the Cell Press journal Current Biology on July 2 have found that people with autism spectrum disorder (ASD) don’t make this natural adjustment like other people do. Autistic children go right on sniffing in the same way, no matter how pleasant or awful the scent.

The findings suggest that non-verbal tests related to smell might serve as useful early indicators of ASD, the researchers say.

“The difference in sniffing pattern between the typically developing children and children with autism was simply overwhelming,” says Noam Sobel of the Weizmann Institute of Science in Israel.

Earlier evidence had indicated that people with autism have impairments in “internal action models,” the brain templates we rely on to seamlessly coordinate our senses and actions. It wasn’t clear if this impairment would show up in a test of the sniff response, however.

To find out, Sobel, along with Liron Rozenkrantz and their colleagues, presented 18 children with ASD and 18 normally developing children (17 boys and 1 girl in each group) with pleasant and unpleasant odors and measured their sniff responses. The average age of children in the study was 7. While typical children adjusted their sniffing within 305 milliseconds of smelling an odor, the researchers report, children on the autism spectrum showed no such response.

That difference in sniff response between the two groups of kids was enough to correctly classify them as children with or without a diagnosis of ASD 81% of the time. Moreover, the researchers report that increasingly aberrant sniffing was associated with increasingly severe autism symptoms, based on social but not motor impairments.

The findings suggest that a sniff test could be quite useful in the clinic, although the researchers emphasize that their test is in no way ready for that yet.

“We can identify autism and its severity with meaningful accuracy within less than 10 minutes using a test that is completely non-verbal and entails no task to follow,” Sobel says. “This raises the hope that these findings could form the base for development of a diagnostic tool that can be applied very early on, such as in toddlers only a few months old. Such early diagnosis would allow for more effective intervention.”

The researchers now plan to test whether the sniff-response pattern they’ve observed is specific to autism or whether it might show up also in people with other neurodevelopmental conditions. They also want to find out how early in life such a test might be used. But the most immediate question for Sobel is “whether an olfactory impairment is at the heart of the social impairment in autism.”

Current Biology, Rozenkrantz et al.: “A Mechanistic Link between Olfaction and Autism Spectrum Disorder” http://dx.​doi.​org/​10.​1016/​j.​cub.​2015.​05.​048