Stem-Cell Therapy Succeeds in Trial
Method Aids Spinal Injuries In Rats, but Technique
May Not Work in Humans
By DAVID P. HAMILTON
Staff Reporter of THE WALL STREET JOURNAL
May 11, 2005
California scientists said they were able to use human embryonic stem cells to repair a particular type of spinal damage in rats, a preliminary but potentially important finding that could help pave the way for clinical trials in people paralyzed by similar injuries.
A team led by Hans Keirstead, a neurologist at the University of California at Irvine, showed that injections of modified human stem cells helped repair an insulating sheath around nerve cells that often is damaged in crushing spinal injuries. When treated with the cells a week after suffering spinal damage, Dr. Keirstead's rats demonstrated significant improvement in their ability to walk.
While the results are a promising sign for the potential benefits of stem-cell research, neurologists and stem-cell scientists cautioned that this particular technique may not work well -- or at all -- in humans. Over the years, researchers have managed to cure paralyzed rats with a variety of different techniques, few of which have yielded effective treatments for people.
In addition, most spinal injuries involve damage to a variety of different tissues, much of which isn't treated by Dr. Keirstead's technique. Some accidents can completely sever the spinal cord, for instance, creating an injury that almost certainly wouldn't respond to this particular stem-cell therapy. The work also suggests that effective treatment in this case is limited to a brief "window" following the initial injury, meaning that Dr. Keirstead's technique may not offer much hope to people who currently are paralyzed.
The research, which appears today in the Journal of Neuroscience, is the first peer-reviewed publication of Dr. Keirstead's work on treating spine-injured rats with embryonic stem cells. Although the scientist has presented preliminary data to colleagues for the last few years, many researchers were unsatisfied and urged him to submit a paper for evaluation by other experts in the field.
Embryonic stem cells, derived from 10-day-old embryos, are potent primordial cells capable of transforming themselves into various types of tissue, such as bone, organs or nerve cells. Scientists have hoped to use such stem cells to treat degenerative conditions such as diabetes or paralysis, in which the body can no longer regenerate tissues ravaged by disease or injury.
Exactly how stem cells "differentiate" into various types of tissue, however, isn't fully understood. Neither are the effects of transplanting the cells into various parts of the body. In their most basic, "undifferentiated" state, for instance, transplanted stem cells can form tumors known as teratomas.
Dr. Keirstead's team first perfected a method for coaxing undifferentiated stem cells to form more specialized "precursor" cells. Under the right conditions, those precursor cells, in turn, can form nerve cells called oligodendrocytes, which form a protective sheath out of a fatty substance called myelin around the axons that conduct nerve signals through the body.
The team deliberately crushed the rats' spinal cords, under anesthesia, in a way that damaged the myelin sheaths. One group of rats received a spinal injection of the precursor cells seven days after the injury; another group received the same injections, but not until 10 months after they were injured.
In both groups, the precursor cells appeared to transform into oligodendrocytes once injected into the rats. Only in the rats treated in the first week, however, did the oligodendrocytes appear to repair the myelin sheaths around damaged nerves. The same rats exhibited significant improvement in various measures of motor control compared to others not treated with stem cells. Rats treated at the 10-month mark didn't reap the same benefits.
Dr. Keirstead's work was funded by Geron Corp., a Menlo Park, Calif., biotechnology company that helped give birth to the field of stem-cell research. David Greenwood, a Geron vice president, said the company has the "hope, if not the expectation" of moving Dr. Keirstead's work into human clinical trials, but declined to say when he expected that to happen.
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