Human Stem Cells Help Rats to Fend Off Lou Gehrig’s Disease
By Rob Waters
Oct. 15 (Bloomberg) — Neural stem cells transplanted into the spinal cords of rats from a human fetus slowed onset of a form of Lou Gehrig’s disease, a condition that attacks the nerve circuits that control movement.
Researchers placed the cells in rats genetically engineered to develop a form of the disease, also know as amyotrophic lateral sclerosis or ALS. The rodents with the cells were slower to show symptoms such as weight loss and diminished strength, and lived about 11 days longer over a 30-month life span.
The finding suggests stem cells can be grafted into damaged nervous systems for a clinical benefit, contradicting the belief of many scientists. It may also eventually offer hope to about 5,600 people in the U.S. who are diagnosed yearly with ALS, which is almost always fatal.
“The dogma was that the spinal cord can not make neurons, or allow engrafted cells to become neurons,” said Vassilis Koliatsos, the Johns Hopkins School of Medicine neurologist who led the study, in an Oct. 12 telephone interview. “The assumption was also that because this is a toxic environment where motor neurons are dying, the cells would die.”
These assumptions “are increasingly proven wrong” by this research and other recent studies, he said. Koliatsos’s study was published today in the journal Transplantation.
The transplanted cells, which developed into neurons, or nerve cells, formed connections to existing neurons that had been damaged by the disease and were able to convey information through electrical signals and deliver proteins to help nourish the sick cells, Koliatsos said.
Neuralstem Inc.
The researchers used a line of neural stem cells developed by Neuralstem Inc., a closely held biotechnology company based in Rockville, Maryland. The company developed the line from fetal tissue donated by a woman who underwent an elective abortion at 8 weeks.
The stem cells, taken from an area near the developing spinal cord of the fetus, have the theoretical ability to develop or differentiate into any of three cell types found in the nervous system. The cells were kept alive in culture and chemically manipulated to keep them from differentiating.
The researchers exposed the spinal cords of the rats and used a tiny micropipette to inject cells. Rats in one group were given about 400,000 living neural stem cells; another control group was injected with dead cells.
The rats that got the live cells began losing weight at about 59 days on average, a week later than the rats in the control group. When made to walk an uphill plank as a strength test, the cell-treated rats performed better over a longer period of time. They also lived to about 86 days, 11 days longer than the control rats.
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When the rats were examined after their deaths, the researchers found that more than 70 percent of the transplanted stem cells had developed into nerve cells, and that many grew endings that connected to other cells, allowing them to transfer nerve impulses that direct muscular action and movement.
“These cells became neurons and they also made connections to sick neurons,” he said. “If you make connections to sick neurons, you close the circuit, you give them information.”
The connections allowed needed proteins and growth factors produced by the new neurons to pass to the damaged cells. This may help solve a problem that has vexed researchers. When scientists have delivered these proteins and growth factors, also known as trophic factors, using drugs, they reached unwanted targets and caused side effects, Koliatsos said.
`Delivers the Goods’
“You use the stem cell as a very complex biological structure or machine that manufactures and sends these trophic factors where they ought to be given,” he said. “It delivers the goods right on target.”
In this experiment, stem cells were injected in the portion of the spinal cord that controls the lower body. The next step, which Koliatsos has already begun working on, is to deliver the cells to the part of the spinal cord that controls upper body motion, including chest wall expansion and breathing.
“We need to do that, see if it’s well tolerated and see if we can extend their survival longer,” Koliatsos said. After that, he said, he’ll start thinking about how to study this type of treatment in people.
About 30,000 Americans have Lou Gehrig’s disease, according to the ALS Association. The disease begins with weakness in the arms and legs, and progresses to paralysis as motor neurons are damaged.
The study was funded by the National Institutes of Health, the Muscular Dystrophy Association and the university’s Robert Packard Center for ALS Research.
To contact the reporter on this story: Rob Waters in San Francisco at rwaters5@bloomberg.net .
Last Updated: October 15, 2006 00:58 EDT
Published: May 30, 2007 at 11:10 AM
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