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David A. Steenblock, D.O.

Inc
Personalized Regenerative Medicine

Snorting Stem Cells

W As media outlets around the world reported this latest development in stem cell
W technology, the opening line of a U.S. News & World Report article began by posing the
following question: "If you had a brain malady that could be treated with stem cells, how
W. would you like them delivered – by having surgeons cut open your skull to implant the
cells, or by snorting them like a nasal decongestant?"
S Anticipating that the latter option might be more appealing than the former, a scientist at
T the University of Minnesota has shown that stem cells suspended in a fluid rapidly
migrate to the brain when inhaled through the nose.
E Dr. William Frey, adjunct professor of pharmaceutics in the College of Pharmacy at the
M University of Minnesota at St. Paul, in collaboration with colleagues in Tuebingen,
Germany, has developed a new stem cell "delivery method" which has applications not
C only for stem cells but also for other therapeutic cells and drugs that cannot easily
penetrate the blood-brain barrier.
E The researchers demonstrated the method in an animal model in which mice were able to
L sniff small droplets of fluid in which adult stem cells that had been derived from rats
were suspended. Within an hour, the rat stem cells were clearly detectable within the
L brains of the mice. In a second experiment, rats sniffed a fluid suspension of cells from
human brain tumors, which were also found to penetrate the brains of the rats within an
M hour.

D. As Dr. Frey explains, "We proved you could noninvasively deliver stem cells to the brain
from the nose. We’ve shown these cells reach the brain intact."
O Dr. Frey and his collaborators have filed a patent application for the invention of this
R "stem cell delivery technology", which works by transmitting the stem cells via the
olfactory nerves of the nose and the small holes that are found in the cribriform plate,
G which is a thin horizontal section of the skull at the base of the brain. The olfactory bulbs
that lie just above the cribriform plate are, in fact, anatomical extensions of the brain.

When researchers combined the stem cells with the enzyme hyaluronidase, which makes
connective tissue more permeable, the efficiency of the migrating stem cells increased.
When the enzyme was not administered, only 584 stem cells out of 300,000 reached the
olfactory bulbs, whereas that number tripled when the enzyme was administered. The
enzyme did not improve the ability of the stem cells to reach the cerebral cortex or other
areas of the brain, however.

According to Frey, "When you cut into the brain, that leads to an inflammatory response.
We’re hoping this will help. We didn’t see evidence that intranasal stem cell treatment
caused inflammation. 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. 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. Therefore,
W we are also looking into the use of antibiotics, anti-inflammatories, and
immunosuppressant’s that may further facilitate the safe delivery of therapeutic cells."
W The next step is to test the intranasal stem cell therapy in an animal model of Parkinson’s
W. or other types of neurological diseases, testing not only for efficacy but also for safety,
especially side effects such as inflammation, infection or immune rejection
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