Hans Keirstead and his colleagues in the Reeve-Irvine Research Center at UC Irvine have found that a human embryonic stem cell-derived treatment they developed was successful in restoring the insulation tissue for neurons in rats treated seven days after the initial injury, which led to a recovery of motor skills. But the same treatment did not work on rats that had been injured for 10 months. The findings point to the potential of using stem cell-derived therapies for treatment of spinal cord damage in humans during the very early stages of the injury. The study appears in the May 11 issue of The Journal of Neuroscience.
"We're very excited with these results. They underscore the great potential that stem cells have for treating human disease and injury," Keirstead said. "This study suggests one approach to treating people who've just suffered spinal cord injury, although there is still much work to do before we can engage in human clinical tests."
Acute spinal cord damage occurs during the first few weeks of the injury. In turn, the chronic period begins after a few months. It is anticipated that the stem cell treatment in humans will occur during spinal stabilization at the acute phase, when rods and ties are placed in the spinal column to restabilize it after injury. Currently, drug treatments are given during the acute phase to help stabilize the injury site, but they provide only a very mild benefit, and they do not foster regeneration of insulation tissue.
For the study, the UCI team used a novel technique they created to entice human embryonic stem cells to differentiate into early-stage oligodendrocyte cells. Oligodendrocytes are the building blocks of myelin, the biological insulation for nerve fibers that is critical for maintenance of electrical conduction in the central nervous system. When myelin is stripped away through disease or injury, sensory and motor deficiencies result and, in some cases, paralysis can occur.
The researchers injected these cells into rats that had experienced a partial injury to the spinal cord that impairs walking ability -- one group seven days after injury and another 10 months after injury. In both groups, the early-stage cells formed into full-grown oligodendrocyte cells and migrated to appropriate neuronal sites within the spinal cord.
In the rats treated seven days after the injury, myelin tissue formed as the oligodendrocyte cells wrapped around damaged neurons in the spinal cord. Within two months, these rats began to show significant improvements in walking ability in comparison to injured rats who received no treatment.
In the rats with 10-month-old injuries, though, motor skills did not return. Although the oligodendrocyte cells survived in the chronic injury sites, they could not form myelin because the space surrounding neuron cells had been filled with scar tissue. In the presence of a scar, myelin could not grow.
These studies indicate the importance of myelin loss in spinal cord injury, and illustrate one approach to treating myelin loss. Keirstead and his colleagues are currently working on other approaches using human embryonic stem cells to treat chronic injuries and other disorders of the central nervous system.
In previous studies, Keirstead and colleagues identified how the body's immune system attacks and destroys myelin during spinal cord injury or disease states. They also have shown that when treated with antibodies to block immune system response, myelin is capable of regenerating, which ultimately restores sensory and motor activity.
Oswald Steward, Gabriel I. Nistor, Giovanna Bernal, Minodora Totiu, Frank Cloutier and Kelly Sharp also participated in the study, which was supported by the Geron Corp., a UC Discovery grant, Research for Cure, the Roman Reed Spinal Cord Injury Research Fund of California and individual donations to the Reeve-Irvine Research Center. Geron provides the human embryonic stem cells for Keirstead's research.
The Reeve-Irvine Research Center was established to study how injuries and diseases traumatize the spinal cord and result in paralysis or other loss of neurologic function, with the goal of finding cures. It also facilitates the coordination and cooperation of scientists around the world seeking cures for paraplegia, quadriplegia and other diseases impacting neurological function. Named in honor of Christopher Reeve, the center is part of the UCI School of Medicine.
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