Transplants in Animal Models Could Translate into Therapy
PA) - Neural stem cells, transplanted into injured brains,
survive, proliferate, and improve brain function in
laboratory models according to research based at the
University of Pennsylvania School of Medicine.
The findings, published in the October edition of the
journal Neurosurgery, suggest that stem cells
could provide the first clinical therapy to treat traumatic
brain injuries. Traumatic brain injuries occur in two
million Americans each year and are the leading cause
of long-term neurological disability in children and
"Transplantation of neural stem cells in mice three
days after brain injury promotes the improvement of
specific components of motor function," said Tracy
K. McIntosh, PhD, professor in the Department of
Neurosurgery, Director of Penn's Head Injury Center,
and senior author of the study. "More importantly,
these stem cells respond to signals and create replacement
cells: both neurons, which transmit nerve signals, and
glial cells, which serve many essential supportive roles
in the nervous system."
If stem cells are blank slates, able to become any type
of body cells, then neural stem cells (NSCs) are slates
with the basics of neurology already written on them,
waiting for signals in the nervous system to fill in
the blanks. The NSCs used by McIntosh and his colleagues
were cloned from mouse progenitor cells and grown in
culture. The advantage of NSCs exists in their ability
to easily incorporate themselves into their new environment
in ways other types of transplants could not.
"If you put these cells into normal newborn mice,
they would behave exactly like normal cells - they create
different neural cell types and they don't reproduce
tumorigenically," said McIntosh. "In humans,
the use of similar neural stem cells would avoid the
ethical dilemmas posed by fetal stem cells and the limitations
seen in cultures of cloned neurons."
In humans, traumatic brain injury is associated with
disabilities affecting mobility, motor function and
coordination. Following NSC transplantation in mice,
the researchers used simple tests to determine motor
skills. They found that mice with transplanted NSCs
recovered much of their physical ability. The transplanted
NSCs, however, seemed to have little effect in aiding
recovery of lost cognitive abilities.
"The ultimate goal, of course, is to translate
what we have learned into a therapy for humans,"
said McIntosh. Neural transplantation has been suggested
to be potentially useful as a therapeutic intervention
in several central nervous system diseases including
Parkinson's disease, Huntington's disease, ischemic
brain injury, and spinal cord injury. While McIntosh
is impressed with the results of NSC transplants in
mice, similar trials for humans are not expected in
the near future.
The lead author on this study is Peter Reiss, MD, a
visiting fellow from the University of Cologne working
in Dr. McIntosh's laboratory. Much of the work was performed
in collaboration with the laboratory of Evan Y. Snyder,
MD, Harvard Medical School.
Other contributing researchers from the Department of
Neurosurgery include, Chen Zhang, MD, PhD, Kathryn E.
Saatman, PhD, Helmut L. Laurer, MD, Luca G. Longhi,
MD, Ramesh Raghupathi, PhD, Philipp Lenzlinger, MD,
Jonathan Lifshitz, PhD, John Boockvar, MD, Grant Sinson,
MD, and M. Sean Grady, MD. Contributing researchers
from outside of Penn include Edmund Neugebauer, MD,
of the University of Cologne, Germany and Yang D. Teng,
MD, from Harvard Medical School.
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