Snorting Stem Cells

By Deane Morrison

If you had a brain malady that could be treated with stem cells, how would you like them delivered—by having surgeons cut open your skull to implant the cells, or by snorting them like a nasal decongestant?

Not really a hard choice, is it?

A University of Minnesota researcher has taken the first step toward making this kind of medical delivery service a reality by showing that when stem cells suspended in fluid are snorted, they rapidly migrate into the brain. William Frey, an adjunct professor of pharmaceutics, and his colleagues in Tuebingen, Germany, describe their work in a recent article in the European Journal of Cell Biology.

The method holds promise for delivering not only stem cells, but other therapeutic cells or drugs that can’t easily penetrate the blood-brain barrier.

The researchers had mice sniff tiny droplets containing adult stem cells from rats. An hour later, rat stem cells were clearly visible in the mice’s brains. To make sure the ability to penetrate the brain wasn’t limited just to those cells, they also had rats snort a second type of cells, from human brain tumors. These cells also penetrated the brain within an hour.

“We proved you could noninvasively deliver stem cells to the brain from the nose,” says Frey, who collaborated with principal investigator Lusine Danielyan of the University Hospital of Tuebingen and others. “We’ve shown these cells reach the brain intact.” 

Frey and his co-inventors have filed a patent on their stem cell delivery technology.

Riding the rails

How did the stem cells get there? They likely traveled to the brain along the olfactory (smell) nerves through small holes in the cribriform plate, a thin horizontal part of the skull at the base of the brain. They also likely traveled inside fluid-filled spaces that surround blood vessels passing from the nose to the brain.

Just above the cribriform plate, olfactory nerves connect to the olfactory bulbs, two round extensions of the brain that process smell. Stem cells were found in the olfactory bulbs and also in the cerebral cortex, cerebellum, and other brain regions.

The migrating stem cells got a boost if the researchers first had the rodents snort an enzyme called hyaluronidase, whose day job is to make connective tissue more permeable. Of approximately 300,000 stem cells administered, an average of 584 reached the olfactory bulbs when the enzyme was not given; when it was, the number nearly tripled. The effect was muted for cells reaching the cerebral cortex and other areas of the brain, however.

Better than boring

Besides the obvious convenience, delivering stem cells intranasally has other advantages over implanting them through a hole in the skull. For example, doctors could easily administer more than one treatment if needed.  

Also, “when you cut into the brain, that leads to an inflammatory response,” says Frey. “We’re hoping this will help. We didn’t see evidence that intranasal stem cell treatment caused inflammation.”

The Food and Drug Administration has yet to approve any stem cell-based therapies for brain disorders. But when used with stem cells that are both safe and therapeutic, intranasal cell delivery may someday be used to treat a variety of brain diseases and conditions, Frey says.

“Intranasal delivery of therapeutic cells could potentially benefit the treatment of head injury, stroke, Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, and so on,” says Frey.  “One of the best ways to treat patients may be with their own cells. For example, the patient’s own bone marrow-derived stem cells could be delivered to produce dopamine, the missing chemical messenger in Parkinson’s disease.”

The next order of business for Frey, Danielyan, and their colleagues is to find out how long snorted stem cells remain in the brain. They also plan to test intranasal stem cell therapy in an animal model of Parkinson’s or another neurological disease to assess both safety and efficacy.

And the researchers want to make sure their technology doesn’t cause any inflammation or infection, or an immune response.

“Therefore, we are also looking into the use of antibiotics, anti-inflammatories, and immunosuppressants that may further facilitate the safe delivery of therapeutic cells,” says Frey.