From University of Florida
UF’S Mcknight Brain Institute researchers: Pioneering spinal cord procedure appears safe GAINESVILLE, Fla. --- 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. 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.
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.
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