Parent Cells Found in Brain May Be Key to Nerve Repair

January 8, 1999: Scientists in Sweden have identified for the first time the parent cells that give rise to many and maybe all of the different cell types in the adult brain.

These neural stem cells, as they are called, are of great interest because, if they could be manipulated appropriately, they would be the obvious repair kit for replacing damaged neural tissues in everything from spinal cord injuries to Parkinson's disease.

The Swedish biologists worked with rats, but now that the cells' hiding place in the rat brain is known, the human counterpart cells are strongly expected to lie in the same place.

Discovery of the cells, announced by Dr. Jonas Frisen and colleagues at the Karolinska Institute in Stockholm in an article published in Friday's Cell, is part of a fundamental change in brain biology.

Until recently it had been thought that the brain never renewed itself or added new cells after gaining its mature form. The belief implied that the brain did not possess stem cells, the source cells from which tissues like blood and skin can constantly renew themselves.

This dogma started to crack when biologists showed in 1992 that a small percentage of cells in brain extracts could divide and develop into the principal types of brain cell. Much work has since been done on brain stem cells acquired by grinding up whole animal brains. But no one knew where in the brain the stem cells come from.

In their paper, Frisen and his team say they have now identified the brain's stem cells.
The cells were already known as ependymal cells, described by one biologist as the most boring cells in the brain because their function is simply to line the cavities of the ventricles and spinal cord which hold the spinal fluid.

These cavity-lining cells are differentiated, meaning that they have taken up a mature form. In contrast, all stem cells identified so far are general, multipurpose cells, uncommitted to any specific fate.

Earlier experiments showed the cavity-lining cells did not divide, confirming their uninteresting nature. But Frisen has found the cells do divide, though at too slow a rate for the earlier tests to detect. Their progeny cells divide rapidly and can differentiate into both neurons and the support cells that are found copiously throughout the brain.

Frisen has found that neurons derived from the cavity-lining cells can migrate from the cavity surface and replace cells in the rat's olfactory bulb or smell-analysis unit, the one brain region known to undergo a rapid turnover of nerve cells.

The Clark Kent/Superman existence of the cavity-lining cells has surprised biologists. "You'd never guess it in a million years," said Dr. Ben Barres, a developmental biologist at Stanford University.

But the identification makes sense, he said, because in the developing embryo the brain cells grow out from stem cells that line a hollow tube. As the organism matures, the tube becomes the ventricles and spinal cord, and the stem cells disappear. It now seems they stay in place but turn into cavity-liners.

Frisen has found that the cavity-lining cells start dividing in earnest when the spinal cord is injured. They then turn into the support cells that make up much of the scar in spinal cord injuries.

"That's really cool because it wasn't clear where the glial cells in scar tissue were coming from," Barres said, referring to the support cells.

Frisen said he hoped to find out how the cavity-lining cells could be induced to make neurons instead of support cells at injury sites. If so, a new approach to spinal cord injury might be developed.

The neural stem cells may also prove relevant to treating Parkinson's disease, which is caused by the death of dopamine-producing cells in a certain region of the brain.
Embryonic cells, such as those derived from fetuses, will develop into these cells if placed in the dopamine region. But ethical problems aside, there are not enough fetuses available to treat everyone.

Frisen said the big advantage of the neural stem cells "is that maybe you could use the patient's own stem cells, avoiding both the ethical and immunological problems."

The cells would be obtained through a biopsy of the cavity-lining cells of the spinal cord, assuming these prove to be the human reservoir of neural stem cells.

Frisen identified the brain stem cells through his studies of spinal cord injuries. He noticed that some of the cells at the injury site were making a substance called nestin, which had been shown by Dr. Ron McKay of the National Institutes of Health to be produced by brain stem cells. The clue made him suspect the cavity-liner cells were also the stem cells, a thesis it has taken four years to establish.

The neural stem cells are descendants of the primordial stem cells that form in the earliest embryo.

By NICHOLAS WADE
Copyright 1999 The New York Times Company
<http://www.nytimes.com/yr/mo/day/news/national/science/sci-stem-cells.html>

janet paterson - 51 now /41 dx /37 onset - almonte/ontario/canada
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