Nov. 29, 1999 (Indianapolis) -- Between 250,000 and 500,000 Americans have spinal cord injuries, and because many of them are young, they will spend decades in a wheelchair unless new treatments can be developed. Research in rats that is being reported in the December issue of the journal Nature Medicine may lead to new therapies in humans.
The neurons that make up the spinal cord have extensions, called axons, that resemble telephone wires and carry messages between the brain and the rest of the body. Traumatic injury can kill neurons or interrupt the axon connections, causing a loss of function. Unlike the heart, parts of the adult spinal cord do not survive transplantation.
In this study, the researchers used embryonic stem cells which have the potential to become any cell type in the body depending on what chemical signals they get when they mature. The researchers hoped that by triggering embryonic stem cells to become nerve cell precursors and then transplanting these precursor cells into the injured area they could promote healing of the spinal cord.
"Establishing regenerative therapies that promote substantial improvements in locomotion when instituted after the injury process is complete has been a difficult obstacle," says John W. McDonald, MD, PhD. McDonald is an assistant professor of neurology at Washington University School of Medicine in St. Louis. "This is a key threshold that had not before been crossed."
The researchers treated rats nine days after an injury to the spinal cord by transplanting stem cells from mice into the injury site. In another control group, the rats underwent a fake operation and were given only the culture medium with no cells.
Two to five weeks following the procedure, the researchers found various markers that showed the transplanted cells were alive and functioning. They also used special techniques to identify any axons that had grown from the transplanted cells. At two weeks, transplanted cells had not only filled the cavity at the point of injury, but had migrated up to 1 cm in each direction. By the five week follow-up, the cells were not as dense but the injured regions still contained mouse axons. None of the cells had developed into tumors.
The researchers also looked at the motor skills of transplanted rats vs. the controls. One month after the surgery, the control rats were not able to move their hind limbs in a coordinated fashion and the limbs could not support their bodies. The hind limbs of the treated animals had regained some movement and were able to partially support the weight of the rats' bodies.
"Their walking certainly wasn't normal," says McDonald. "But this functional recovery was especially encouraging because the cells were transplanted nine days after the spinal cord injury -- a time period that had not yet been explored."
W. Dalton Dietrich, PhD, tells WebMD that he thinks the well done study reports new data regarding strategies to promote recovery of function following spinal cord injury in rats. Dietrich is the scientific director of the Miami Project to Cure Paralysis at the University of Miami School of Medicine.
"Strategies including stem cell transplantation may some day be used to treat paralysis after spinal cord injury," says Dietrich, who was not involved in the study. "The behavioral improvement seen with delayed transplantation is extremely important from the clinical perspective. Whether stem cells or other transplantation strategies represent the best strategy to enhance recovery after spinal cord injury remains to be determined."
Dennis J. Maiman, MD, PhD, stresses that these results are preliminary. While very exciting, he notes that there are still many problems that could arise. Maiman is the medical director of the Spinal Cord Injury Center at the Medical College of Wisconsin in Milwaukee.
"The biggest issue of all may be that human motor behavior is more complicated," says Maiman. "Even if cells grow, it does not mean they will work. Also, in the real world, you often have to contend with blood, scarring, and other problems that were not mimicked in this model."
- In a preliminary study, researchers have transplanted the embryonic stem cells of mice into rats with spinal cord injuries.
- The transplanted cells did survive and grow, improving movement in the injured rats.
- In humans, transplanting stem successfully does not guarantee the cells will function normally.