Injections of human stem cells seem to directly repair some of the damage caused by spinal cord injury, according to research that helped partially paralyzed mice walk again.
The experiment, reported Monday, isn’t the first to show that stem cells offer tantalizing hope for spinal cord injury — other scientists have helped mice recover, too.
But the new work went an extra step, suggesting the connections that the stem cells form to help bridge the damaged spinal cord are key to recovery.
Surprisingly, they didn’t just form new nerve cells. They also formed cells that create the biological insulation that nerve fibers need to communicate. A number of neurological diseases, such as multiple sclerosis, involve loss of that insulation, called myelin.
"The actual cells that we transplanted, the human cells, are the ones that are making myelin," explained lead researcher Aileen Anderson of the University of California, Irvine. "We’re extremely excited about these cells."
The research is reported in Monday’s issue of Proceedings of the National Academy of Sciences.
Stem cells are building blocks that turn into different types of tissue. Embryonic stem cells in particular have made headlines recently, as scientists attempt to harness them to regenerate damaged organs or other body parts. They’re essentially a blank slate, able to turn into any tissue given the right biochemical instructions.
But they’re not the only type of stem cell. Anderson and colleagues used fetal neural stem cells, a type that are slightly more developed than embryonic stem cells because they’re destined to make cells for the central nervous system.
The researchers injured the spinal cords of mice and nine days later injected some with the human neural stem cells.
Four months later, the treated mice could again step normally with their hind paws. Mice given no treatment or an injection with an unrelated cell showed no improvement.
The question was what sparked that improvement. Injections of stem cells might simply stimulate the body to produce some healing factor, or they might directly repair damage themselves.
So Anderson injected the animals with diphtheria toxin, which kills only human cells, not mouse cells. The improvements in walking disappeared, suggesting it was the cells themselves responsible for recovery.
"It was striking," Anderson said.
Finally, the researchers analyzed the actual mouse spinal cords to see what the human stem cells had turned into. The hope was that they would make neurons, or nerve cells, and some did.
But the bulk of the injected stem cells formed oligodendrocytes, a different type of cell that forms myelin, the insulation coating that is key for nerve fibers to transmit the electrical signals they use to communicate.
The toxin step was key to ensuring the transplanted cells themselves are functioning, and all researchers must provide such evidence because different types of stem cells almost certainly will work by different mechanisms in different tissues, said Dr. Doug Kerr, a Johns Hopkins University neurologist who is performing similar spinal cord research with embryonic stem cells.
Much more research must be done before testing stem cells in people with spinal cord injuries, cautioned Anderson. One question is how soon after an injury cells must be administered to have any effect — no one knows how nine days in a mouse’s life correlates to the post-injury period for a person. Also, the mice were bred to avoid immune system destruction of the human cells, and suppressing a person’s immune system because of similar transplant rejection risk poses big problems.
"The last thing we want to do is take someone who’s living a productive life — if confined, we all understand that — and make them worse," said Anderson, who said the work also shows the need to study all types of stem cells. "The exciting part is the potential is there."
The research was funded by the nonprofit Christopher Reeve Foundation and the National Institutes of Health. StemCells, Inc. of Palo Alto, Calif., provided the fetal-derived stem cells.
