February 20, 2008
Stem Cell Therapy Repairs Brain Damage
Stroke-disabled animals improved their ability to walk after getting transplants derived from human embryonic stem cells, raising the prospect that it may someday be possible to help heal victims of the devastating brain injury.
A new study from a team of researchers at Stanford University offers tantalizing hope for recovery from an injury that disables 750,000 Americans every year -- and for which there is no substantive treatment.
"This offers the very exciting potential to treat patients with a cellular therapy that can repair tissue," said lead investigator Gary Steinberg, professor of neurosurgery at Stanford University School of Medicine.
"In the past, it was thought that once brain cells die they can't regenerate. Now we know that brain repair does happen, although not enough," he said. "Now with a therapy of putting in new cells, there is great hope that people will be able to recover from stroke in a meaningful way."
This study, published in today's issue of the journal Public Library of Science-ONE, marks the first time researchers have used human embryonic stem cells to generate neural cells that grow well in the lab and improve animals' physical abilities.
The transplanted cells did not form tumors, as feared. Nor did they cause seizures, another dangerous side effect.
Scientists explained that the transplanted cells may not act as replacements, but instead help nurse the injured brain back to health. The new cells
secrete chemicals that help the brain recover -- perhaps by stimulating new blood vessel formation or by promoting the growth of new neural pathways.
"What we think they are doing is working like little factories, producing factors that improve the environment for recovery," said Steinberg, whose work is funded by the National Institutes of Health.
Stanford researchers will work with the U.S. Food and Drug Administration to start manufacturing these cells in greater quantities, to "scale up" production for testing in other animals -- and someday, perhaps humans.
Because it is possible to grow these cells in bulk, it raises the prospect of an ongoing source of therapy, said scientists.
"The great thing about these cells is that they are available in unlimited supply and are very versatile," said senior scientist Marcel Daadi.
Still, the team warned that it could be five years before the same approach is considered for human testing. And even if successful, it is likely to offer the greatest benefit to new patients, not those with longstanding permanent damage.
What is a stroke?
Stroke is caused by a disruption in the flow of blood to part of the brain because of either a blocked or ruptured blood vessel. The death of brain cells causes paralysis, speech and sensory problems, memory and reasoning deficits, coma and, often, death.
There are no effective treatments for improving the residual disabilities resulting from stroke. Drugs called thrombolytics can reduce damage -- but less than 5 percent of patients get them in time to help.
The new cells are the laboratory-grown progeny of human stem cells harvested from the brains of donated aborted fetuses.
The Stanford team grew the embryonic stem cells in a broth of growth hormones that nudged the cells to mature into stable neural stem cells.
Over time, with further coaxing, these neural stem cells matured into three families of brain cells -- neurons, astrocytes and oligodendrocytes.
How study worked
The cells were injected into the brains of 10 laboratory rats with an induced form of stroke that left one forelimb weak. This injury parallels the type of damage experienced by human stroke victims. They were put in a part of the brain that was adjacent to the most damaged part, but which still had some surviving tissue.
The new cells migrated to the damaged regions of the brain, perhaps sensing trouble. Then they incorporated into the surrounding tissue and began to help repair damage. To prevent possible rejection, rats were treated with an immunosuppressant drug. The new cells stayed alive and functional.
After two months, the rats were scored on leg use, compared with untreated animals. Rats that received the stem cells were able to use their forelimbs more normally than untreated injured rats. Researchers who scored the tests did not know which mice had received injections.
Scientists are now examining the brains of the rats to better understand the process of recovery.
The Stanford scientists used a cell line approved by President Bush. Non-embryonic cells have been shown to improve some function of damaged brains, but these cells are not diverse enough and are not amenable for large-scale production.
Previous studies have shown that stem cells can halt spinal motor neuron degeneration and restore function in animals with spinal cord injury or amyotrophic lateral sclerosis. However, this study is the first to show that transplanted neurons can help against stroke.
Embryonic stem cells are valued by researchers for their ability to become any kind of tissue a body might need. Much research on stem cells has focused on how to get these cells to turn into a heart cell, a kidney cell, a bone cell or whatever is needed to help sick patients.
But this new study joins a growing body of work that indicates these versatile cells can help indirectly, as well, by secreting potent chemicals that can make tissues rejuvenate themselves.
On the Net:
Public Library of Science (PLoS) One Full Report
Stanford University School of Medicine