Cells Identified for Spinal-Cord Repair Could Lead to Nonsurgical Treatment for Injuries

The research, reported in the July 2008, issue of the journal PLoS Biology, was conduced by Dr. Konstantinos Meletis, a postdoctoral fellow at the Massachusetts's Institute of Technology (MIT; Cambridge, MA, USA) Picower Institute, and colleagues at the Karolinska Institute (Stockholm, Sweden). Their findings could lead to drugs that might reestablish some degree of mobility to the 30,000 individuals worldwide afflicted each year with spinal-cord injuries.

In a developing embryo, stem cells differentiate into all the specialized tissues of the body. In adults, stem cells perform similar to a repair system, replenishing specialized cells, but also maintaining the normal turnover of regenerative organs such as skin, blood, or intestinal tissues. The very small numbers of stem cells in the adult spinal cord proliferate slowly or rarely, and fail to promote regeneration on their own. But recent research demonstrates that these same cells, grown in the lab and returned to the injury site, can restore some function in paralyzed rodents and primates.

The researchers at MIT and the Karolinska Institute discovered that neural stem cells in the adult spinal cord are limited to a layer of cube- or column-shaped, cilia-covered cells called ependymal cells. These cells comprise the thin membrane lining the inner-brain ventricles and the connecting central column of the spinal cord. "We have been able to genetically mark this neural stem cell population and then follow their behavior,” Dr. Meletis noted. "We find that these cells proliferate upon spinal cord injury, migrate toward the injury site, and differentiate over several months.”

The study revealed the molecular process underlying the exciting results of the rodent and primate and goes one step further: By identifying for the first time where this subpopulation of cells is found, they have led a way toward modifying them with drugs to enhance their inborn capability to repair damaged nerve cells.

"The ependymal cells' ability to turn into several different cell types upon injury makes them very interesting from an intervention aspect: Imagine if we could regulate the behavior of this stem cell population to repair damaged nerve cells,” Dr. Meletis said.

Upon injury, ependymal cells proliferate and migrate to the injured area, generating a mass of scar-forming cells, plus fewer cells called oligodendrocytes. The oligodendrocytes restore the myelin, or coating, on nerve cells' long, slender, electrical impulse-carrying projections called axons.

"The limited functional recovery typically associated with central nervous system injuries is in part due to the failure of severed axons to regrow and reconnect with their target cells in the peripheral nervous system that extends to our arms, hands, legs, and feet,” Dr. Meletis said. "The function of axons that remain intact after injury in humans is often compromised without insulating sheaths of myelin.”

If scientists could genetically engineer ependymal cells to produce more myelin and less scar tissue after a spinal cord injury, they could potentially avoid or reverse many of the debilitating effects of this type of injury, according to the researchers.

Related Links:
Massachusetts's Institute of Technology
Karolinska Institute