For release: Monday, September 13, 2010
In a study in animals, researchers have shown they can improve recovery from spinal cord injuries through an infusion of cells that help rebuild the myelin sheath – a covering around nerve fibers.
There are an estimated 10,000 to 12,000 spinal cord injuries every year in the U.S. These injuries sever or crush the nerve fibers that run through the spinal cord, potentially leading to complete paralysis and loss of sensation below the level of the injury.
A traumatic blow to the spinal cord also typically causes a loss of myelin and the death of cells that make myelin, which are called oligodendrocytes. Myelin is needed to insulate the electrical signals transmitted by nerve fibers. Despite efforts by many investigators to develop therapies that target myelin, there has been a lack of consensus about the extent to which myelin loss has functional consequences in spinal cord injury.
The new study addressed this issue. It was led by Qilin Cao, M.D., associate professor of neurosurgery at the University of Texas Medical School in Houston, and Scott Whittemore, Ph.D., professor of neurological surgery at the University of Louisville School of Medicine in Kentucky.
The National Institute of Neurological Disorders and Stroke (NINDS) provided major funding for the work.
Writing in the Journal of Neuroscience,* the researchers reported that they could improve recovery in rats with spinal cord injury by giving the animals transplants of oligodendrocyte precursor cells (OPCs). The transplants were most effective when the OPCs were genetically modified to make a growth factor that stimulated their survival, growth and maturation into oligodendrocytes.
Drs. Cao and Whittemore and their team isolated OPCs from the healthy adult rat spinal cord. They also created a population of OPCs carrying the gene for ciliary neurotrophic growth factor (CNTF), after establishing that CNTF is a potent inducer of OPC survival and maturation. They injected these genetically modified OPCs into rats eight days after a spinal cord injury, at several sites near the injury. For comparison, some rats were given a sham injection, grafts of skins cells carrying the CNTF gene, or grafts of OPCs carrying a control gene. At seven weeks post-transplant, the modified OPCs significantly improved the animals’ rate of recovery, based on recordings of electrical activity in the spinal cord as well as behavioral tests.
The researchers also showed that the majority of transplanted OPCs matured into oligodendrocytes, which wrapped around nerve fibers to form myelin. Importantly, the extent of myelin repair was closely matched to the recovery of movement in the animals’ hind limbs.
This close correlation “underscores the importance of remyelination in behavioral improvement” after a spinal cord injury, the researchers wrote.
“There has been controversy about the extent to which demyelination contributes to the loss of function after spinal cord injury, and therefore doubts regarding the benefits of therapies to stimulate myelin repair,” said Naomi Kleitman, Ph.D., a program director at NINDS. “This study provides strong evidence that such an approach is indeed beneficial in an animal model of spinal cord injury.”
- By Daniel Stimson, Ph.D.
Image Caption: Oligodendrocytes (blue) wrap around nerve fibers to form myelin.
*Cao Q et al. “Transplantation of Ciliary Neurotrophic Factor-Expressing Adult Oligodendrocyte Precursor Cells Promotes Remyelination and Functional Recovery after Spinal Cord Injury.” Journal of Neuroscience, 24 February 2010, Vol. 30, pp. 2989-3001.
Last Modified September 14, 2010