Stem
Cell Shakes - Brain scientists have found a solution for how
to turn stem cells into the kind of nerve cells they want. (12/12/02)
Unclogging
the Brain - Just like traffic jams clog a city's roads, sometimes
proteins in our body break down and clog up our cells. When this
happens in our brain, it leads to devastating illnesses. (11/1/02)
Elsewhere on the web
“Manhattan
Project” of Stem Cell Research
Stem
Cells Reduce Brain Damage
NIH
Stem Cell Information
United Cerebral
Palsy Association
More than 400,000 children and adults in the United States suffer from the
brain disorder cerebral palsy.
As this ScienCentral News video 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.