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Scientists Form Brain Cells From Bone Marrow

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TIMES MEDICAL WRITER

In a development that may eventually render moot the debate over use of fetal cells in brain therapy, researchers have succeeded in transforming stem cells from bone marrow into functioning brain cells in rats and humans.

Although the research is at a very early stage, researchers say the dramatic advance may make it possible to use a patient’s own stem cells to treat a variety of brain disorders, including Parkinson’s, Huntington’s and Alzheimer’s diseases, as well as stroke and spinal cord injuries.

Brain tissue from aborted fetuses is now being used experimentally to treat such conditions and shows great promise, but the supply of fetal tissue has been restricted and its use is highly controversial because of the source.

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The discovery “essentially circumvents all the ethical concerns with the use of fetal tissues,” said Dr. Ira Black of the University of Medicine and Dentistry of New Jersey, who reports the finding in today’s Journal of Neuroscience Research.

Stem cells that have the ability to grow into any type of cell found in the body normally are found only in fetuses. But recently, researchers identified a variety of other, more developed stem cells in adults--in the brain and in blood, for example--that have the capability to grow into limited types of tissues.

Black and his colleagues used a variety of chemicals to redirect the growth of these cells into tissues they do not normally produce.

They now are transplanting the cells into rat brains to see whether they are therapeutic, and tests in humans are several years away, he said.

With the discovery, “we have a potentially inexhaustible reservoir of new neurons,” said Dr. Gilman Graves of the National Institute of Child Health and Human Development. “This is very exciting.”

“The possibilities for spinal and brain repair suggested by this study are quite profound,” said Susan Howley, director of research for the Christopher Reeve Paralysis Foundation, which co-sponsored the research with the National Institutes of Health.

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Bone marrow normally is thought of as the source of stem cells that grow into red and white blood cells. But the stem cells Black worked with, also found in the bone marrow, go well beyond that and usually grow into cartilage, bone, muscle and fat.

However, they apparently are even more versatile than researchers had suspected. Just last month, other scientists reported that the stromal stem cells could be converted into liver tissue.

Nonetheless, “it’s quite remarkable that they can be converted into brain cells,” Graves said.

The trick, as is the case in most studies with stem cells from any source, is trying to figure out how to persuade the primordial cells to grow into specific types of tissue. Black said the process is “1% insight and 99% luck and trial and error.”

Black developed a system in which stromal stem cells from rats are treated with a combination of antioxidants and a growth promoter called basic fibroblast growth factor.

No one is sure yet how the combination of chemicals works, but they convert more than 80% of stem cells grown in culture into neurons, a surprisingly high percentage. “These and other stem cells are far more flexible than we had thought a few years ago,” Black said. “It means that we have to rethink what we learned in medical school: that the . . . fate of a cell is fixed.”

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The altered cells sprout axons and dendrites, characteristic growths that appear on the surface of brain cells. They also produce proteins that are normally found only in neurons.

Black and his colleagues then found that they could achieve the same thing with stromal stem cells isolated from humans.

The New Jersey researchers are now transplanting the altered cells into various areas of the brain and spinal cord in rats. “We know that, at the very least, they can survive within the spinal cord for well over a month,” Black said. “That tells us that they are user-friendly in the live animal.”

Now they are attempting to determine whether the cells can become integrated into the host’s nervous system, as fetal tissues have been shown to do.

But he couldn’t speculate on when human studies might begin. “Once we’ve completed the first phase of animal work, we’ll be in a much better position to at least provide a realistic time frame. We have to complete the live animal work to even take an educated guess.”

Dr. Dennis Choi, of the Washington University School of Medicine in St. Louis, cautioned that it is too early to declare the new technique an unqualified success. It may be, he said, that the stromal stem cells already might have developed some characteristics that would prevent them from becoming fully effective nerve cells.

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“It may turn out that stem cells derived from the brain are better than these, or vice versa, or that there is no difference,” Choi said. “All these things remain to be seen.

“But the idea that we can get these cells from bone marrow is really pretty cool.”

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