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The Art of Growing Brain Cells

American and Israeli research teams turn human stem cells into neural precursor cells

MONDAY, Dec. 10, 2001 (HealthDayNews) -- American and Israeli research teams report they've developed similar methods for turning human embryonic stem cells into the predecessors for almost any kind of brain cell.

Both sets of scientists produced cultures made almost entirely of neural precursor cells that they then implanted in the brains of newborn mice. With refinements, the researchers say they hope their methods lead to treatments for a variety of human neurological diseases. The studies appear in the Dec. 1 issue of Nature Biotechnology.

Stem cells are master cells that can become any type of cell in the body. The embryonic cells in the U.S. study belong to one of the stem cell lines approved by the government, and did not involve cloning.

For stem cells to be used for therapeutic purposes, they must be nudged into becoming the specialized type of cells that researchers require. In recent years, scientists have learned how to make blood, liver, bone and muscle cells this way.

"What we did is to coach the [stem cells] towards a specialized fate," says Dr. Su-Chun Zhang, lead author of the American study. "In other words, to make them become cells that would only generate brain cells."

To trigger the process, Zhang and his colleagues at the University of Wisconsin's Stem Cell Research Program placed stem cells in a culture containing a growth factor that encouraged the cells to start becoming neurons. The stem cells stayed in that mixture for roughly eight to 10 days.

Then the researchers removed the evolving stem cells, using an enzymatic reaction that separates neural precursor cells from non-neural cells. This produced a solution made up of approximately 95 percent neural cells, which they then implanted in the brains of mice.

"We call them precursor cells because these cells can further generate mature neurons and glial cells, which we would expect in the brain," Zhang says. "Also, we have demonstrated that they can give rise to different kinds of neurons that produce different signaling molecules, like neurotransmitters."

For example, some of the neural cells in the mice became neurons with markers suggesting they could produce dopamine, the neurotransmitter implicated in Parkinson's disease.

At this stage, Zhang doesn't know whether this method can produce every specific kind of neural cell. And although the neural cells produced in this study appear to be normal, it's not yet clear whether they function. He says future studies will determine that.

Transplanting the cells into mice also let the researchers see whether the cells contained substantial populations of non-neural cells, such as bone, muscle or fat. "We did not see those types of tissues after transplantation," Zhang says.

The transplant also relieved another concern for the researchers.

"The worry for stem cells is that if the cells are not differentiated and you transplant stem cells, they will form tumors," Zhang says. "We did not see that happen."

If the cells develop into brain cells, and prove they work in animal models for Parkinson's disease, Huntington's disease or multiple sclerosis, it could lead to human trials, Zhang says.

In the second study, conducted at the Agnes Ginges Center for Human Neurogenetics at the Hadassah University Hospital in Jerusalem, researchers left the stem cells in culture for three weeks, letting them grow in an undifferentiated state.

They then removed clusters of cells with markers of becoming neural cells, and gave them two growth factors. The result: highly purified concentrations of neural precursor cells.

Dr. Lorenz Studer, chief of the Laboratory of Stem Cell & Tumor Biology at Memorial Sloan-Kettering Cancer Center in New York, says both groups have created neural stem cells.

"Clearly, in both cases, the major contribution is that they were able to get one very specific cell type out of … some human embryonic stem cells," Studer says. "They could get the cells in very high purity."

It's an important achievement, he adds, because stem cells in culture normally differentiate in a more chaotic way, creating something resembling a tumor.

"With this novel technique, they can harness the potential of these embryonic stem cells," he says. "Neural cells have potential for brain repair."

Before that can happen, the researchers need to perfect their methods, Studer says. He cautions that these findings are still years away from having a clinical impact.

What to Do: Check out this stem cell primer from the National Institutes of Health, or visit the American Association for the Advancement of Science or Scientific American.

SOURCES: Interviews with Su-Chun Zhang, M.D., Ph.D., investigator, Stem Cell Research Program, Waisman Center, and assistant professor, departments of neurology and anatomy, University of Wisconsin, Madison; Lorenz Studer, M.D., chief, Laboratory of Stem Cell & Tumor Biology, and assistant professor, departments of neurosurgery and cellular biochemistry & biophysics, Memorial Sloan-Kettering Cancer Center, New York City; Dec. 1, 2001, Nature Biotechnology
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