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Transplanted Neural Stem Cells Migrate Throughout The Abnormal Brain, Reduce Disease Symptoms

Date:
June 9, 1999
Source:
NIH-National Institute Of Neurological Disorders And Stroke
Summary:
For years, researchers have probed the mysteries of neural stem cells -- immature cells that can differentiate into all the cell types that make up the brain -- with the idea that they might be useful for treating brain disorders such as Parkinson's disease. Important new animal research now suggests that these cells may be effective in treating a much broader array of brain diseases than previously anticipated, including Alzheimer's disease and many childhood brain disorders.

For years, researchers have probed the mysteries of neural stem cells -- immature cells that can differentiate into all the cell types that make up the brain -- with the idea that they might be useful for treating brain disorders such as Parkinson's disease. Important new animal research now suggests that these cells may be effective in treating a much broader array of brain diseases than previously anticipated, including Alzheimer's disease and many childhood brain disorders.

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The new study, led by Evan Snyder, M.D., Ph.D., of Children's Hospital and Harvard Medical School in Boston, provides the first evidence from studies in animals that neural stem cells can be used to repair damage from brain disorders such as adrenoleukodystrophy and multiple sclerosis, where cell dysfunction is "global" or spread throughout the brain. Investigators previously believed that the promise of these cells was limited to disorders such as Parkinson's disease in which damage is restricted to defined areas of the brain. While preliminary, the new findings raise exciting possibilities for future therapies. The study was funded in part by the National Institute of Neurological Disorders and Stroke (NINDS) and appears in the June 8, 1999, issue of the Proceedings of the National Academy of Sciences (PNAS)(1).

"Stem cells that can develop into a variety of different types of nerve cells and glial cells would be extremely valuable in the therapy of acute and chronic neurological disorders," says Gerald D. Fischbach, M.D., director of NINDS. "The current study shows that stem cells of a certain type can become distributed widely throughout the brain." Glial cells are non-neuronal cells which play supporting roles in the brain and nervous system.

In the new study, Dr. Snyder and his colleagues injected cultured neural stem cells into the brain ventricles of newborn mice from a mutant strain that develops severe tremors by 2 to 3 weeks of age. The tremor develops because the mice lack a key protein needed to make myelin, the insulating coating that surrounds nerve fibers. The lack of normal myelin in these mice mimics the defect seen in many human demyelinating disorders, such as multiple sclerosis and a group of childhood disorders called leukodystrophies. The researchers found that most of the transplanted cells migrated throughout the brain and matured into normal-looking oligodendrocytes, the brain cells that produce myelin. These oligodendrocytes produced a significant amount of the missing protein and began to cover nearby nerve fibers with myelin just as normal oligodendrocytes would. Moreover, tremors disappeared almost completely in 60 percent of the tested mice that received the transplants.

Intriguingly, the neural stem cells transplanted into the brains of the mutant mice were much more likely to form oligodendrocytes than were neural stem cells transplanted into the brains of normal mice. This suggests that the neural stem cells somehow sense that an oligodendrocyte-produced factor is missing in the mutant mice and attempt to compensate for the problem. A similar study previously found that neural stem cells transplanted into mice missing a particular type of neuron tended to form that neural cell type more frequently than expected. If confirmed, this ability to compensate for missing cell types could make neural stem cells a much more effective therapy than researchers anticipated.

While this study looked only at a model of demyelinating disease, Dr. Snyder believes it is plausible that neural stem cells will react to cues from the brains of animals or humans affected with other diseases and compensate for the defects associated with those diseases as well. It may also be possible to genetically engineer neural stem cells so that they not only replace lost cells throughout the brain -- as is seen in Alzheimer's disease -- but also produce proteins that correct whatever problem made the original brain cells die. "Sometimes the original cells are overly sensitive to stress from toxins, viral infections, or other problems because of missing or damaged genes. If so, transplanted cells with normal genes could withstand the stress," says Dr. Snyder. "Researchers also can engineer neural stem cells to withstand, neutralize, or even protect other cells against a toxin or other threat."

While neural stem cell research is very promising, researchers still need to show that human neural stem cells behave like their mouse counterparts, says Dr. Snyder. They also need to learn whether the benefits shown in young animals extend to older animals and whether transplanted cells can overcome ongoing degenerative disease processes so that they do not become new victims of that degeneration. Follow-up research is also needed to better understand how transplanted cells are directed to grow throughout the brain and compensate for missing brain proteins.

Dr. Snyder is now testing neural stem cells in animal models for many other disorders, including perinatal asphyxia (which can lead to cerebral palsy), Krabbe's disease (a demyelinating disorder), and stroke. If all goes well, these studies could eventually lead to clinical trials. However, it is too early to say which human disorders might be the first to be targeted with neural stem cell therapy, and it will take years of careful clinical tests before researchers can show conclusively whether the stem cells work in human disease.

The NINDS is the nation's premier supporter of research on the brain and nervous system. It is part of the National Institutes of Health in Bethesda, Maryland, and will celebrate its 50th anniversary in the year 2000.


Story Source:

The above story is based on materials provided by NIH-National Institute Of Neurological Disorders And Stroke. Note: Materials may be edited for content and length.


Cite This Page:

NIH-National Institute Of Neurological Disorders And Stroke. "Transplanted Neural Stem Cells Migrate Throughout The Abnormal Brain, Reduce Disease Symptoms." ScienceDaily. ScienceDaily, 9 June 1999. <www.sciencedaily.com/releases/1999/06/990609073135.htm>.
NIH-National Institute Of Neurological Disorders And Stroke. (1999, June 9). Transplanted Neural Stem Cells Migrate Throughout The Abnormal Brain, Reduce Disease Symptoms. ScienceDaily. Retrieved November 22, 2014 from www.sciencedaily.com/releases/1999/06/990609073135.htm
NIH-National Institute Of Neurological Disorders And Stroke. "Transplanted Neural Stem Cells Migrate Throughout The Abnormal Brain, Reduce Disease Symptoms." ScienceDaily. www.sciencedaily.com/releases/1999/06/990609073135.htm (accessed November 22, 2014).

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