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Thread: Stem cell research: Through the nose

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    Stem cell research: Through the nose

    Stem cell research: Through the nose
    U of L team excited about possibilities for Parkinson's, spinal-cord injuries
    By Patrick Howington
    The Courier-Journal

    Dr. Welby Winstead extracted tissue samples for nasal stem cell research. Winstead used an endoscope to remove a tiny piece of the olfactory lining.

    University of Louisville researchers are looking in a novel place for new ways to treat Parkinson's disease and spinal-cord injuries.

    Deep inside the nose, at the spot where scents are relayed to the brain, are stem cells thought to hold the potential for repairing damaged nervous systems.

    But unlike those from embryos, these stem cells aren't politically controversial. And unlike other nervous-system stem cells in adults, these can be retrieved without risky procedures such as brain surgery.

    They are in a tiny patch of nasal lining -- the only part of the nervous system exposed to the outside world.

    ''I reasoned a number of years ago that perhaps (we could) harvest stem cells'' from the lining, said the team's principal investigator, Fred J. Roisen. ''I wouldn't say it's easy, but it's certainly less surgically invasive to go into your nasal cavity'' than the brain.

    The stem cells have been shown to produce two types of nerve cells that could one day be used to help damaged spinal-cord nerves regrow, if U of L researchers can continue unlocking their secrets.

    Any use in human patients would be several years off, and only after overcoming many challenges.

    But the cells could be useful much sooner to researchers and drug companies looking to test how new drugs affect nerve cells.

    That's why Psychiatric Genomics, a Maryland drug-discovery firm, recently agreed to pay U of L up to $250,000 for licensing rights on cell lines from the research. It also provided a research grant of almost $80,000.

    Richard Chipkin, the company's CEO, said the cells U of L is working with ''have great potential for being a renewable source'' of stem cells.

    The cells have been reproducing themselves at U of L for two years now -- building a stockpile for possible research by entities like Psychiatric Genomics, which seeks cures for psychiatric illnesses.

    ''It would be very interesting if you could compare the cells from someone who has no mental disorder with the cells from someone who has schizophrenia, or bipolar disease, or depression,'' Chipkin said.

    The research's main funding is from the National Institutes of Health, because of its potential to help heal spinal-cord injuries. It is one of five U of L projects sharing an $8.5 million spinal-research grant awarded two years ago.

    The U of L project is the only one known to be using nasal stem cells from adults, as researchers seek alternatives to those from embryos.

    Most research has focused on stem cells taken from embryos because they can turn into virtually any type of human cell.

    But the use of embryos has drawn fire from anti-abortion groups, and last year President Bush ruled that government-financed researchers could work only with existing human embryonic stem-cell cultures, rather than create new ones.

    Embryos also had been the logical choice because researchers only recently discovered that stem cells found in adults could also be developed into specialized cells.

    ''The fact that adult stem cells have even some of the capacity of embryonic stem cells is kind of radical compared to what thinking was five years ago,'' said Jane Roskams, an olfactory-system expert at the University of British Columbia's Centre for Molecular Medicine and Therapeutics.

    Recently, though, results of experiments with adult stem cells from various parts of the body, including the bone marrow and brain, have been promising.

    The U of L research focuses on cells from the olfactory epithelium -- the nasal-cavity lining that enables smelling.

    The lining contains ''a cell population that can divide throughout life, whether you're at 95 years or two years,'' Roisen said.

    In other words, the cells have a sort of immortality. They also routinely produce new olfactory neurons to replace those damaged by nosebleeds or airborne chemicals.

    To search for the stem cells, Roisen's team first took olfactory lining from cadavers donated to U of L.

    In a relatively small percentage of cases, they were able to locate the stem cells and get them to grow.

    The next, more difficult step was to harvest cells from living people. That task fell to Dr. Welby Winstead, an ear, nose and throat surgeon and assistant professor at U of L.

    While performing nasal sinus surgery on patients, Winstead used an endoscope to remove a tiny piece of the olfactory lining. The patients had volunteered for the biopsy.

    Then Roisen's lab worked with the tissue trying to identify and isolate stem cells and get them to grow.

    More often than not, it didn't work -- either because the bit of lining Winstead removed didn't contain stem cells, which aren't clustered in one place, or because researchers couldn't make them grow.

    But in two patients, out of about 15, the cells were found and grown. That, plus the instances of success with cadavers, convinced Roisen and Winstead that their approach has promise.

    ''It's chilling, almost. Because that's very close to the meaning of life, or whatever we're dealing with here,'' Winstead said. ''That's why there's a lot of excitement.''

    Susan Hines, a surgery patient who let Winstead biopsy a piece of her olfactory lining, said she's glad she did.

    ''It didn't really put me at any greater risk,'' she said. ''I thought, 'This is a good way that I'm going to help somebody down the road.' ''

    The U of L team currently only has permission to extract cells from Winstead's surgery patients, though it expects to seek a wider range of volunteers in the future.

    The challenge goes beyond locating the stem cells and getting them to grow in culture; scientists must also manipulate them to morph into a desired type of gene. That's not easy.

    Roisen's team has gotten the extracted stem cells to reproduce themselves endlessly -- every 18 to 20 hours -- and to produce two types of cells, neurons and glia.

    While neurons transmit nerve impulses, glia provide a supporting environment, insulating and nurturing neurons and improving their connections. If the U of L team could coach the stem cells to produce more glia, that could one day help damaged spinal-cord or other nerve cells repair themselves, Roisen said.

    The team's research is still in an early stage. It has injected some cells into mice to see if they will thrive there, Roisen said, but ''we have not had any really positive results where we've taken a paralyzed animal and put the cells in, or anything like that. We're far from that.''

    But he is encouraged by the results of an experiment in Italy, involving stem cells taken from the human olfactory bulb at the base of the brain. When they were transplanted into mice that had Parkinson's-like symptoms, the mice recovered.

    The cells the Italian team used have the same origin as those produced by Roisen's team.

    Dr. Wolfram Tetzlaff, a spinal-cord expert at the University of British Columbia who has reviewed Roisen's research, called it ''exciting'' and very interesting.
    Given the nasal cells' accessibility, ''one could envision that a patient's own stem cells . . . might be used in the future to replace lost ones,'' said Tetzlaff. He recently published findings that nerve cells in rats' brains that were thought to die after spinalcord injury could be regenerated a year later.

    Ron McKay, an NIH stem-cell expert who led research to produce dopamine-making cells from embryonic stem cells, cautioned that work with adult stem cells is still young.

    He said that while embryonic stem cells have been found capable of turning into cells useful in treating disease, ''we're missing that evidence'' with adult stem cells.

    But he added that the U of L research is interesting and that ''with a bit of good fortune and some hard work, they may do something quite valuable here.''

    [This message was edited by seneca on Jul 31, 2002 at 11:54 PM.]

  2. #2
    Senior Member alan's Avatar
    Join Date
    Jul 2001
    Baltimore, MD
    My nose is NOT off-limits. I hope this bears fruit.

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