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Adult Tissue Can Yield Stem Cells, Researchers Say

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TIMES SCIENCE WRITER

Neural stem cells, which promise treatments for currently incurable brain ailments and spinal cord injuries, may be far easier to obtain from adult tissues than anyone had thought, new research released Sunday indicates.

Potent but politically charged, neural stem cell research may prove to be the first effective way to undo the damage of spinal cord injuries, strokes and a host of debilitating brain diseases such as multiple sclerosis.

The findings were presented Sunday at the Society for Neuroscience in New Orleans, which represents 28,000 scientists who study the biology of the brain.

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Taken together, the new research encompasses progress against conditions that affect millions and offers a heady glimpse of a world, perhaps a decade away, when the abilities of neural stem cells have been harnessed to routinely rejuvenate nerve tissue in the spine and the brain. Today, however, scientists are just beginning to master these cells.

“What we are trying to do is extraordinarily ambitious--to reconstruct a damaged brain,” said molecular biologist Ronald McKay at the National Institute of Neurological Disorders and Stroke. “Stem cell technology is going to be absolutely critical.”

Now, however, stem cells are extracted from human embryos or fetal tissue. The need to use cells derived from the products of abortion or from human embryos created for research purposes raises formidable ethical and regulatory challenges to wider use of the cells.

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Federally funded embryo research was effectively banned until last August. Then the Clinton administration ruled that publicly funded experiments could be conducted on the about 150,000 human embryos left behind at fertility clinics, provided that federal money is not used to actually destroy the embryos.

But a new study by researchers at the Robert Wood Johnson Medical School in New Jersey shows for the first time that, with the proper experimental growth factors, stem cells isolated from adult bone marrow can convert into neurons quickly and can be grown in almost unlimited supply.

Moreover, animal experiments show that these cells can be successfully transplanted into the spinal cord and brain, where the cells appear to survive and connect to other neurons, the researchers said.

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The discovery raises the prospect that people in need of treatment one day might be able to donate their own cells to repair crucial nerve tissue damaged by stroke, disease or injury, eliminating any need for powerful drugs to suppress the recipient’s immune system.

“We were somewhat overwhelmed,” said lead researcher Dr. Ira Black, who is head of Robert Wood Johnson’s neuroscience department. Bone marrow “appears to be a robust source of cells. There may be a variety of [other] easily accessible sources of cells that can generate neurons.”

In a similar laboratory advance reported Sunday, researchers led by Fred H. Gage at the Salk Institute for Biological Studies in La Jolla grew neural cells from human tissue donated after death from people up to 72 years old. Two other independent laboratory experiments indicate that neural cells can even be grown from skin and scalp tissue from living donors.

“The research shows that the [cadaver] tissue could be a new, noncontroversial source of human neural cells for transplantation and experimentation,” said Gage.

The age at which the stem cells were harvested, however, did appear to make a crucial difference. Adult stem cells are biologically less potent than embryo cells. Cells cultivated from older donors did not last as long in the laboratory as those taken from younger donors, nor did they divide and multiply as efficiently. “Clearly the cells that are younger divide more easily,” Gage said. “There is no substitute for youth, at least so far.”

Other studies released at Sunday’s meeting show for the first time that neural cell transplants can restore movement abilities lost to brain injury, stroke, paralyzing diseases and spinal cord injuries. In experimental implants with laboratory animals, the neural cells also appeared to be naturally attuned to injuries and automatically sought out damaged brain or spinal tissue.

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In a series of new studies and experiments presented Sunday, scientists demonstrated the scope and the promise of new advances in the quest to harness stem cells. New studies show that:

* Stem cells from human embryos can generate an almost limitless supply of a specific type of nerve cell that supplies the neurotransmitter dopamine needed to help those with Parkinson’s disease. Transplants with fetal cells have shown some success but further work has been limited by the availability of the right type of neural cells, said McKay, who conducted the study.

* Stem cell transplants can help restore movement in mice with traumatic brain injuries like those suffered by 2 million Americans every year. “The animals that received the stem cell transplants got better,” said Tracy McIntosh, director of the head injury center at the University of Pennsylvania, where the research was conducted. “The improvement was quite marked.” The transplants involved neural stem cells cultivated from mouse embryo cells.

* Stem cell transplants, combined with the application of special growth factors, can restore movement skills often lost or impaired as a consequence of strokes. Dr. Evan Snyder and his colleagues at Harvard Medical School, who performed the research, also discovered that the stem cells moved on their own from the back of the brain, where they were injected, to the stroke-damaged area in the front of the brain. “Stem cells seem to be able to sense an injury,” Snyder said.

* Stem cell therapy appears to restore the protective nerve sheathing often damaged as a result of multiple sclerosis or in some spinal injuries. Jeffrey Kocsis at Yale University, who did the study with colleagues at Sapporo Medical College in Japan, reported that “we got anatomical repair” of injured spinal cord tissue.

Other researchers at Johns Hopkins University reported that stem cell transplants appeared to help paralyzed lab animals recover the kind of movement ability often lost as a result of motor neuron diseases such as amyotrophic lateral sclerosis (ALS), which affects as many as 20,000 people in the United States.

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Researchers involved in these new studies said that the first feasibility and safety studies with human patients might begin within three years. But they cautioned that they still don’t know nearly enough about how to create and control these powerful cells.

“There is a lot of exciting data,” said Dr. Jeffrey Rothstein, a leading stem cell researcher at Johns Hopkins in Baltimore. “But it is one thing to grow a set of cells in a laboratory and quite another thing to have a therapeutic agent.”

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