제  목 : Cultured Neural Stem Cells Reduce Symptoms in Model
  일  자 : 1998년 07월
  제공처 : Internet

                     Cultured Neural Stem Cells
        Reduce Symptoms in Model of Parkinson's Disease
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     For decades, researchers have imagined treating human diseases by
     replacing damaged cells with stem cells - embryonic cells from which all
     other kinds of cells develop. While the potential benefits are enormous,
     such strategies have been limited by an uncertain supply of stem cells.
     Now, scientists have shown that neural stem cells can be multiplied and
     raised to maturity in the laboratory and that these cells can greatly
     reduce symptoms in an animal model of Parkinson's disease.

     The study is the first to show that neural stem cells grown outside the
     body can form specific kinds of neurons - in this case,
     dopamine-producing cells - and that these neurons can survive and
     function normally when they are transplanted into the living brain.
     Dopamine is an important nerve signaling chemical, or neurotransmitter,
     and the loss of dopamine-producing cells in one region of the brain is
     responsible for the symptoms seen in Parkinson's disease. The new finding
     suggests that cells multiplied in culture may ultimately prove useful in
     treating Parkinson's and other nervous system diseases. It also provides
     new opportunities for studying how the brain develops that may greatly
     improve understanding of nervous system disorders, says Ronald McKay,
     Ph.D., of the National Institute of Neurological Disorders and Stroke
     (NINDS), senior author of the report which will appear in the August 1998
     issue of Nature Neuroscience.1

     "Cells are the ultimate device for delivering substances to the brain, so
     this could become one of the most widely used therapies in medical
     research," says Dr. McKay.

     Unlike the original cells of the embryo, which can form literally any
     kind of cell, neural stem cells are restricted to becoming nervous system
     cells. However, they still can develop into all the types of cells that
     make up the brain and spinal cord. The process in which cells that start
     out with unlimited potential fates develop into specific types of mature,
     non-dividing cells is called differentiation.

     In the new study, Dr. McKay and his colleagues Lorenz Studer, M.D., and
     Viviane Tabar, M.D., took neural stem cells from the brains of rat
     embryos and grew them in culture dishes with a protein called basic
     fibroblast growth factor that helps the cells survive and divide. After
     the cells multiplied for 6 to 8 days, the growth factor was removed and
     the cells were allowed to aggregate into free-floating spheres of
     neurons. The neurons in the spheres began to develop functioning
     connections with each other, producing dopamine as well as several other
     kinds of neurotransmitters. When the spheres were injected into the
     brains of rats that were missing the dopamine-producing region on one
     side of their brains, the rats' Parkinsonian symptoms gradually
     diminished. Most showed about a 75 percent improvement in motor function
     80 days after they received the transplants.

     At present, the cells can be multiplied only 10 to 100 times, not enough
     to provide a good supply of stem cells for routine use in the clinic.
     "We've opened a door, but it's not yet clear that you can drive a truck
     through it," says Dr. McKay. However, he believes it may soon become
     possible to expand stem cells as many as 10,000 times. If so, thousands
     of patients might ultimately be treated with cells derived from one
     source. This enhanced supply of cells would make clinical trials much
     more feasible while reducing the ethical concerns associated with use of
     embryonic tissue. The ability to grow neural stem cells in the laboratory
     also provides an excellent opportunity for genetically manipulating the
     cells to improve their chances of surviving and connecting to the rest of
     the brain after transplantation. For example, scientists might be able to
     manipulate neural stem cells so that they produce not only dopamine, but
     also growth factors that enhance cell survival and integration.

     If all goes well, cultured neural stem cells could be applied in human
     clinical trials in the next 2 to 3 years, Dr. McKay says. The biggest
     obstacle to this type of therapy now may be controlling what the cells do
     once they are injected, he adds. For example, they might die, grow the
     wrong connections, or even form tumors if conditions are not exactly
     right.

     Several groups of clinical investigators are already studying whether
     human embryonic dopamine-producing cells can effectively treat
     Parkinson's disease. More than 200 patients have received transplants of
     these cells. However, the potential for this type of therapy to become
     widely available has always been limited by difficulty in obtaining
     embryonic tissue. The new study shows that it now may be possible for
     researchers to grow their own easily controlled supply of stem cells.

     While the new procedure has great promise for improving treatment of
     neurological disorders, it also will be important in helping researchers
     understand how the brain develops. The neural stem cells in this
     experiment went through all the basic steps of brain development outside
     of the body - they multiplied, differentiated, and formed functioning
     connections with other cells. By manipulating cells in culture during
     these crucial stages, researchers could study how complex brain
     structures are built, damaged, and rebuilt, allowing them to thoroughly
     test many theories about how these processes occur. Culturing stem cells
     also will allow researchers to test different strategies for enhancing
     production of specific kinds of cells and improving how those cells
     integrate with the brain once they are transplanted. For example, the
     cultured cells could be temporarily arrested in their development so that
     they are "primed" for integration when they are transplanted into the
     brain.

     The NINDS, one of the National Institutes of Health located in Bethesda,
     Maryland, is the nation's leading supporter of research on the brain and
     nervous system and a lead agency for the Congressionally designated
     Decade of the Brain.

     1Studer, L.; Tabar, V.; and McKay, R.D.G. "Transplantation of expanded
     mesencephalic precursors leads to recovery in Parkinsonian rats." Nature
     Neuroscience, Vol. 1, No. 4, August 1998, pages 290-295.

     This release will be posted on EurekAlert! at http://www.eurekalert.org
     and on the NINDS home page at http://www.ninds.nih.gov/whtnwhp.htm.