Cell Transplants in Rats Restore Brain Function
and Lessen Further Damage in The Brain
PA) - University of Pennsylvania researchers have found
that by transplanting neural progenitor cells into rats
with brain injuries they can restore brain function
and lessen further brain damage. Their findings are
the first to demonstrate the ability of progenitor cells,
grown in culture, to restore cognitive and motor function
while rescuing brain cells from the cumulative effects
of traumatic brain injury.
The results of the research, led by Tracy K. McIntosh,
PhD, of the University of Pennsylvania School of Medicine,
is presented in the May issue of the Journal of Neurosurgery.
"Stem cell transplants are currently of interest
because of the potential they have for treating brain
injuries in humans," said McIntosh, professor in
the departments of Neurosurgery, Bioengineering, and
Pharmacology and director of Penn's Head Injury Center.
"In this study we have determined how progenitor
cells - a more developed type of stem cell - cannot
only restore function, but counteract the secondary
injuries that result from brain trauma."
Unlike stem cells, which are completely unspecialized,
progenitor cells have begun the path to specialization.
In this study, the stem cells used have become progenitor
brain cells, although they have not yet developed into
a specific type of brain cell. The researchers found
that the progenitor cells were able to survive in the
hostile environment of the injured brains and actually
promote the reconnection of brain pathways that were
destroyed during trauma. Using tests to determine cognitive
ability and motor skills, rats with the transplanted
progenitor cells recovered substantially better than
rats that did not have the transplanted cells.
The researchers used two different types of cultures
of the same progenitor cells. One type remained 'naïve;'
that is, they had not been altered, while the other
had been transfected with a gene to produce Nerve Growth
Factor (NGF). As the name suggests, NGF is an enzyme
that induces nerve cells to grow.
"We had originally hypothesized that the NGF-producing
cells would be more capable of regenerating brain function,"
said McIntosh. "We were surprised to find that,
in terms of nerve growth, both types of cells performed
The NGF-producing cells, however, had an additional
effect - they protected against further damage in the
The destruction of brain tissue does not stop after
the initial head impact. Cells in the brain weaken and
continue to die from the cumulative effects of the injury
in a process called apoptosis, a series of internal
reactions that causes the cells to die. The rats that
received the NGF-producing cells retained a significant
amount of brain cells after transplant than the rats
that received just the naïve cells.
According to McIntosh, in addition to promoting nerve
growth, NGF also induces brain cells to produce more
antioxidant enzymes, which remove the free radicals
that may trigger apoptosis. "The NGF-producing
cells provide cells with an added resistance against
the dangerous environment of an injured brain,"
said McIntosh. "And so we have the combined strength
of a growing progenitor cell and a nice supply of a
molecule that ensures that the cells continue to thrive."
The research presented in this study is a collaborative
effort between researchers at Penn and counterparts
in Sweden and Spain, with whom McIntosh began an association
as a Fullbright Fellow on sabbatical in Europe. Other
contributing researchers include Tadeusz Wieloch, PhD,
Anders Bjorklund, PhD, Gustav Mathiasson, PhD, and Gregor
Tomasevic, PhD, from Lund University, and Alberto Martinez-Serrano,
PhD, of the Autonomous University of Spain. Other Penn
researchers include Matthew F. Phillips, MD, Philipp
Lenzlinger, MD, Grant Sinson, MD, and M. Sean Grady,
For the last decade, McIntosh and his colleagues at
Penn's Head Injury Center have been investigating the
effects of brain injury and possible treatments. Each
year, approximately 100,000 people die from traumatic
brain injuries, and 500,000 more are permanently disabled.
Every 15 seconds, someone, usually a young person, suffers
from a brain injury.
"Sadly, it is an epidemic that most people do not
realize exists," notes McIntosh, "and to date,
there is no clinical treatment that can effectively
treat the damage."
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