Stem cells repair rat spinal cord damage.

Among the challenges of medicine, spinal cord injury ranks high. Nerve cells in the spine don't regenerate naturally, and attempts to revive or repair a damaged cord have met with frustration. To bypass this problem, researchers have recently tried animal experiments replacing ruined nerve cells in animals with transplants of fetal cells. This technique has shown promise, but only when experimenters perform the transplant within a few days of an injury.

Researchers at Washington University School of Medicine in St. Louis now report that they have restored leg movement in injured rats by transplanting cells into the injury site 9 days after the rats received a crushing blow to the spine. The scientists used mouse-embryo stem cells modified to ensure they would grow into basic nerve cells and associated cells.

When the spine is severely bruised, some nerve cells die off immediately. A second wave of programmed cell death called apoptosis follows. Most of this carnage occurs within 24 hours, shutting off nerve signals traveling the spine, says study coauthor John W. McDonald, a physician and neuroscientist at Washington University.

The center of the bruised spine fills with fluid, becoming a cyst. Later, scar tissue piles up, preventing recovery. Neurons at the injury site stop functioning, as do their elongated extensions, called axons. Even if a neuron remains intact, it often dies quickly if the trauma has stripped the protective sheath, a fatty protein called myelin, off its axon.

The blunt injury that the researchers used in the rat experiment "stimulates the majority of [traumas] seen in people who have spinal cord injuries," McDonald says. He and his colleagues studied 62 rats whose spines were bruised and that could not support weight on their back legs. Nine days after injury, 28 of the rats each received injections of roughly 1 million embryonic stem cells pretreated with retinoic acid to induce their growth into nervous system cells. Coauthor David I. Gottlieb, a neurobiologist also at Washington University, devised the pretreatment.

Rats given stem cell injections regained the ability to stand on four legs and walk, albeit not perfectly, within 2 weeks, McDonald says. In 34 rats receiving no cell transplants, the hind legs remained crippled, the researchers report in the December 1999 NATURE MEDICINE. All rats received drugs typically used to prevent rejection of transplants.

Examination of the rats after 2 and 5 weeks showed that most of the transplanted stem cells had died off, but that enough had survived for the animals to have a growing supply of new nervous system cells, McDonald says. In the treated rats, the researchers observed some new neurons with axons that extended up to 1 centimeter away from the injection site.

The researchers also found two other kinds of nervous system cells--oligodendrocytes and astrocytes--thriving at the injury site in the treated rats. Oligodendrocytes form the myelin sheaths that protect axons, much like plastic coating insulates electric wires, and speed the signals that travel along axons. Astrocytes are star-shaped cells that provide the scaffolding upon which neurons can grow.

It's unclear how the transplant restored leg movement.

In the rats, about 60 percent of the daughter cells of the injected stem cells were oligodendrocytes, 20 percent were astrocytes, 10 percent were neurons, and 10 percent were various other types of cells, McDonald says.

"That sounds like a good mix, because you will need oligodendrocytes ... to remyelinate the tissue," says Wolfgang J. Streit, a neuroscientist at the University of Florida Brain Institute in Gainesville.