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Building Brain Bridges

http://www.sciencentral.com/news/articles/view.php3?language=english&type=article&article_id=218391867

January 21, 2003
by  Sanjanthi Velu
ScienCentral News

More than 400,000 children and adults in the United States suffer from the brain disorder cerebral palsy.

As this ScienCentral News video (requires RealPlayer) reports, neurologists may have found a way to use stem cells to bridge the gaps in the brains of those affected.

The Injured Brain

Many diseases and disorders of the central nervous system involve the degeneration of nerve cells, or neurons. Although there are some treatments for the temporary relief of symptoms there is as yet no cure. Research on stem cell biology offers hope for those who suffer such incurable diseases of the brain and nervous system, such as Parkinson’s Disease, Lou Gehrig’s Disease (amyolateral sclerosis, ALS), multiple sclerosis, and Alzheimer’s Disease—where cell loss is the principal cause—as well as a variety of disorders in children and infants, such as cerebral palsy and mental retardation.

Specialized cells in the brain called neural stem cells (NSCs) have the potential to develop into any type of cell in the brain or spinal cord. In a study published in the journal Nature Biotechnology, lead author and neurologist, Evan Snyder, at Burnham Institute in California, found that NSCs—when layered on a microscopic, synthetic scaffold and transplanted into the injured brain—are attracted to the neurodegenerative environment where they regenerate, fill large cavities in the brain with brain tissue, and seem to replace the dead or dysfunctional cells.

Snyder conducted most of his research at Harvard Medical School where he spent 22 years as a pediatrician. He recently moved to Burnham Institute to head the new stem cell research project there. In an earlier study, Snyder and his colleagues at Harvard found that stem cells were effective in stopping the slow degeneration of brain function in mice with brain injuries that mimic the process of aging or Parkinson’s disease in people. The transplanted cells in that case were found to rescue the damaged host cells and stimulated them to generate dopamine-producing cells, which are lost in patients affected by Parkinson’s disease.

Repairing Cerebral Palsy

In the current study, Snyder and his colleagues at Harvard decided they would approach “a truly massive (brain) injury, an injury where huge amounts of tissue are lost.” So they studied a type of injury that is a common cause of cerebral palsy, a brain disorder in children that affects about 10,000 babies each year in the United States, according to the Centers for Disease Control and Prevention. Snyder says that although there are many different types of cerebral palsy, and each has it’s own cause, “some types of cerebral palsy seem to emerge because of insufficient amounts of blood flow or oxygen to a particular part of the brain. And as a result those parts of the brain will die.” Such extensive brain tissue loss destroys large amounts of cells and their connections, causing malfunctions in those parts of the brain and eventually leading to a loss of muscle coordination.

So the researchers set out to find whether NSCs can heal injuries in mice missing large parts of the brain similar to tissue loss in the human condition of severe cerebral palsy. Snyder soon found that the NSCs themselves were unable to rebuild the lost tissue as the holes in the brain were too big, and the cells were not able to gain a foothold in these wide spaces. There was also no template or pattern to guide the stem cells to reconstruct the brain. But the team found that the stem cells’ regenerative ability was much improved when they were seeded into a tiny, synthetic, biodegradable scaffold before transplantation. Snyder says the scaffold “ maintains the cells in this space—in this crevice—long enough for complex communications to take place. And as the cells get a foothold in the damaged brain, and start sending out these long connections into the damaged brain, the damaged brain starts sending connections into these cells, and they start interacting with each other and filling in the missing gaps of brain tissue with various kinds of cells.” These include neurons and glial cells, which are the supporting cells. Then the scaffold degrades and dissolves. In addition, inflammation or scarring from this process was also significantly reduced.

Pros and Cons

Snyder says the advantages of using a scaffold are that it does its job and disappears in a very seamless, unobtrusive way. “Sometimes people have reported that this dissolving process itself causes damage or injury,” he says. “And this is something we’ve not observed, particularly with the kind of scaffold that we’ve been using.” However, he warns that, “One complication you really have to be very vigilant for is the development of a tumor—uncontrolled division of the cell.”
Even though they have not seen this complication so far during their tests in animals, Snyder stresses that we need to wait and watch the progress of the stem cell growth in animals for as long as possible to see if there is any tumor formation. And when the process is ready for human trials, Snyder says, “we may want to put something we call a suicide gene into the cell, so that even many, many years down the line if we see a problem emerge, even a low likelihood of the problem, we can trigger the suicide gene in those cells so they would self-destruct.”

Snyder cautions that another problem that needs to be addressed is the possibility that the stem cells may crowd out the normal cells, or take over areas that they really shouldn’t be in. And that, he says, “might cause malfunctioning because the cells that should be there are no longer there and the cells that shouldn’t be there are not doing the proper job.”
In spite of the cons, this kind of a marriage between stem cell biology and tissue engineering reveals a potential self-repair process in the central nervous system without extensive genetic or molecular manipulation of either the stem cells or the host cells. And it brings hope of a new treatment for those suffering from cerebral palsy or severe brain damage.

The work was supported in part by grants from The March Of Dimes, National Institutes Of Neurological Diseases And Stroke, Project ALS, The Stem Cell Research Program Of The Korean Ministry Of Science And Technology, and CMB-Yuhan Grant Of Yonsei University College Of Medicine Research Fund of 1998.
 

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