http://unisci.com/stories/20013/0910013.htm
10-Sep-2001
University of Florida researchers
report in the September issue of the Journal of Neurotrauma that it is
both feasible and apparently safe to implant human embryonic tissue in
people with spinal cord injuries.
The findings could help lay the groundwork
for future efforts to treat spinal cord injury with other types of cell
transplants.
In their first peer-reviewed analysis
of a small pilot study that attracted international attention when it began
in 1997, the scientists say that the initial two U.S. patients with spinal
cord injuries to undergo the procedure have experienced no ill effects.
"We didn't set out to cure spinal
cord injury in this clinical trial," said Douglas K. Anderson, chairman
of the UF College of Medicine's department of neuroscience and a career
research scientist with the Malcom Randall Veterans Affairs Medical Center
in Gainesville. "Instead, we were looking to determine whether it was feasible
to transplant this tissue into the spinal cord and whether it was procedurally
safe to do so. We've found that it is."
Nine surgeries were performed on
eight patients at Shands at UF medical center from July 1997 to February
2000. In two journal articles, the research team reports on how the first
two patients fared during the first 18 months after transplantation.
Neurosurgeon Dr. Richard G. Fessler,
now based at the Chicago Institute of Neurosurgery and Neuroresearch, transplanted
about a teaspoonful of tissue into their spinal cords in connection with
a needed operation to drain and close fluid-filled cavities that had developed
after their initial injuries.
The condition, called syringomyelia,
is thought to occur in up to 20 percent of people with spinal cord injuries.
It can cause unbearable pain and progressive loss of sensation and movement.
The hope was that the transplanted
tissue, consisting of developing spinal cords obtained from aborted fetuses
6 to 9 weeks old, would grow enough to keep the cavities filled and prevent
any further deterioration of the patients' conditions.
The scientists have found some signs,
but no conclusive proof, that the tissue did indeed plug the cavities.
"We were looking for evidence that
the graft tissue survived and was able to grow and at least partially fill
these holes," said Dr. Edward D. Wirth III, a UF assistant professor of
neuroscience who is the lead author on one of the journal articles. "But
all we can tell for certain from magnetic resonance images is that the
cysts were indeed collapsed where we placed the tissue.
"The MRI images do not enable us
to distinguish between host tissue and transplant tissue, so we can't say
for certain that the transplant tissue survived."
(The graft tissue, which otherwise
would have been discarded, was obtained from health-care facilities not
affiliated with the university.)
Though the UF findings are likely
to be of interest mainly to the scientific community, the insights researchers
have gained could help shape early high-profile efforts to explore cellular
transplants to treat diseases or injuries.
A variety of cell types -- including
the much-discussed embryonic stem cells and the more specialized adult
stem cells -- are considered possible candidates for future transplants.
"We were looking at using embryonic
spinal cord tissue as a template for other materials that might become
available," said Paul J. Reier, a professor of neuroscience and neurosurgery.
"But before you go through the arduous task of refining the use of other
cell lines at the laboratory bench, we wanted to find out if you can even
do these kinds of transplants in any way, shape or form.
"By doing this limited study, it
put us on a learning curve. We went from bench to bedside, and now with
what we've learned, we're going back to the bench."
For 18 years leading up to the pilot
study, Reier and colleagues had been investigating in laboratory animals
whether embryonic tissue could help repair injured spinal cords. The theory:
The implanted tissue could provide a bridge that could connect healthy
sections of the cord, thereby restoring communication along the body's
main channel for transmitting nerve system signals.
After noting promising results in
rats and cats, the UF team designed a small study to test the procedure's
feasibility and safety in humans.
Since their transplant surgeries,
the first two patients have remained neurologically stable, Wirth said.
Tests analyzed by Floyd J. Thompson,
an associate professor of neuroscience, revealed that the first patient
had experienced a decrease in the excessive firing of the nerve cells in
his lower spinal cord. Such excessive firing is thought to be a source
of spasticity in patients with spinal cord injuries. The patient, however,
had reported a sensation of increasing spasms in his right leg.
"One possible explanation is that
the patient had an overall increase in the sensations he was receiving
from his leg," Wirth said.
Thompson, lead author of the second
journal article, said the studies "confirmed that the neural circuit evaluation
procedures that we have been developing in the laboratory over a 10-year
period were procedurally safe to use, provided important quantitative information
and opened new questions that we have taken back to the laboratory."
Before the surgery, the second patient
had been experiencing pain in his upper back and right arm, but it went
away immediately after surgery and has never returned, Wirth said.
Because the pain went away so soon
after the operation, it appears that it was related to the draining of
the fluid from the cavity rather than the transplant, Wirth said. "But
since the pain has not returned, it suggests that the transplant didn't
cause any harm."
For now, the UF and Shands teams
are not planning additional transplant surgeries. In the laboratory, the
scientists are tackling numerous issues related to spinal cord repair.
Among other efforts, scientists in Reier's laboratory are investigating
the use of human cell lines not derived from either embryos or fetuses.
"Before this study, there wasn't
a whole lot being translated from the basic science laboratory to the clinical
setting," Anderson said. "The field needed an icebreaker.
"We used embryonic tissue because
it had been backed up by years of research in animal models. But we've
always known that tissue would not be ideal for a bigger clinical trial
because of its limited availability and a very narrow window in which it
remains viable.
"The long history of preclinical
work has not been done in stem cells or any other cell lines, but now scientists
can do these kinds of basic studies. With what we know now, it will help
us design the experiments that will help us do that research and move this
effort forward."
Reier and Anderson hold professorships
endowed by cattle rancher Charlie Mack Overstreet of Kathleen, Fla., and
his family.
[Contact: Victoria White]
Copyright © 1995-2001 UniSci
By Victoria White
The scientists, who are based at
the Evelyn F. and William L. McKnight Brain Institute of UF, plan to report
on the others when they have finished collecting and analyzing that data.