Human Stem Cells Aid Rats With ALS

MDA grantee Vassilis Koliatsos at Johns Hopkins University in Baltimore recently coordinated a team of scientists who transplanted human stem cells into the spinal cords of rats with amyotrophic lateral sclerosis (ALS) and obtained significant benefit.

ALS is a progressive, paralyzing disease of adulthood that usually leads to death within three to five years of onset. Some 10 percent of cases are inherited, but the vast majority have no known cause.

The findings, published in the Oct. 15 issue of the journal Transplantation, may have implications for the future of stem cell transplantation in ALS and other disorders of the motor neurons, the nerve cells in the brain and spinal cord that control muscle movement.

The investigators grafted human fetal spinal cord stem cells into the lumbar (lower back) spinal cords of rats with a genetic form of ALS and then measured the cells’ ability to mature, as well as their effects on motor neuron numbers, motor performance, disease onset and survival in the animals.

The rats received the immunosuppressive drug FK506 (tacrolimus) to prevent rejection of the cells.

The human cells showed extensive maturation into neurons, which then made contact with existing nerve cells. They also produced two neurotrophic (nerve-nourishing) proteins, glial cell-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF), as mature neurons normally do.

The grafts delayed the onset and progression of the ALS-like disease and extended the life span of the rats by more than 10 days, even though the cells were inserted only into the lumbar area and not into vital areas, such as those that control breathing.

“The potency of this effect can be best appreciated if one considers the fact that, for a disseminated [widespread] illness like ALS, lumbar cord grafting is a partial approach that omits other vital portions of the [cord], i.e. the cervical motor neuron column responsible for respiratory [muscle] movements,” the authors write.

The scientists concluded that stem cell grafts can survive well despite being in an environment where cells are degenerating (which has until now been open to debate) and can exert “powerful clinical effects.” They say at least some of these effects may be related to the secretion of neurotrophic factors, which can probably travel over relatively long distances, rather than to new neuron formation or new cell-to-cell connections.