Harnessing ‘smell’ to heal skin

Olfactory receptors in the nose that allow us to smell are also present on the surface of keratinocytes. According to new research, stimulating a particular receptor with a specific synthetic sandalwood oil causes those keratinocytes to proliferate and migrate, processes that are essential to wound healing and skin regeneration.

Our sense of smell begins when airborne molecules dock with about 350 different and very specific types of olfactory receptors (ORs) located in the nose. This sends signals along nerves directly to the brain where they are integrated into patterns we learn to recognize as our morning coffee or the baby’s diaper needing a change.

It turns out that ORs are not restricted to the nose, about 150 different types have been identified on a variety of the twenty or so tissue cell types that they have examined, from the prostate, liver and gut to the skin. Cell physiologist Hanns Hatt, M.D., Ph.D., and his lab at the Ruhr University Bochum, Germany, has been studying these ORs, trying to figure out what molecules are able to dock with each receptor type and then understand the signaling cascade triggered by that interaction.

The first one he identified a few years back was on spermatozoa. The molecule that fits the receptor like a key slipping into a lock is a synthetic version of what the nose recognizes as lily of the valley. Dr. Hatt tells Dermatology Times the research “showed that this odorant influenced the movement and speed of human sperm cells.”

Next: Zeroing in on sandalwood oil

Selecting sandalwood oil

Dr. Hatt says 15 to 20 different olfactory receptors are expressed on human keratinocytes, the most notable of which is OR2AT4. They began screening a hundred structurally different odorant molecules to see which might fit into this receptor.

Sandalwood oil has an ancient history of being used in perfumes, skincare products and aromatherapy, but it is rare and expensive, so synthetic variants have been developed to meet the demand. The lab screened 10 different synthetic variants of sandalwood and later one version of the natural oil.

Sandalore was the most potent in activating the targeted OR when cultured with keratinocytes for five days. The synthetic sandalwood is sold in small bottles for aromatherapy and in larger quantities for commercial use. Dr. Hatt says the molecule increased cell proliferation by 32 percent and cell migration by nearly half.

One other synthetic generated a lesser effect while two appeared to be antagonists. The remaining synthetics and natural sandalwood oil seemed to have no meaningful effect on keratinocytes.

The lab also tested the compounds against skin cultures and biopsies.

“We made a scratch with a knife and watched how long it took the wound to heal. It was about one-third faster” with Sandalore present, Dr. Hatt says.

There was a dose response in the 10-micromolar range, which he calls “a relatively low concentration.” And the keratinocytes also exhibited a sensitization, he says.

“You can apply it multiple times and the response gets bigger,” Dr. Hatt says.

Next: Potential for usable products

Creating a usable product

All of this leads Dr. Hatt to believe it will be possible to turn these proof of concept findings into a usable product.

“Perhaps we will be able to add a sandalwood oil odorant to a topical cream to make wounds heal faster,” he hypothesizes, “or use it to regenerate aging skin.”

Joel Mainland, Ph.D., a researcher at the Monell Chemical Senses Center in Philadelphia, says, “There is a huge trend toward odor receptors being found elsewhere in the body, so I’m not surprised by that.”

But he is surprised by what they are doing in the skin.

“A lot of people have thought that odor receptors were doing minor chemical detection,” he says, “but this specific system, wound healing, is certainly a new and exciting example of this broader trend.”

University of Miami dermatologist Robert S. Kirsner, M.D., Ph.D., calls the study “very interesting. It represents a novel target and potentially opens up a whole new realm to stimulate growth, or possibly inhibit growth, in wound healing.”

Dr. Mainland cautions against over-exuberance. He says that while there is a lot of commonality in human ORs, “We see about 30 percent of olfactory receptors are different between two individuals.” At the genetic level, “If you have one amino acid change in the receptor, it can change or destroy the function of it.”

So it might be that an odorant molecule that triggers wound healing activity in one patient might have little or no effect for another.

Reference:

Busse D, Kudella P, Grüning NM, Gisselmann G, et al. J Invest Dermatol. 2014 Jul 7. [Epub ahead of print]