http://www.reutershealth.com/archive/2001/11/12/eline/links/20011112elin003.html

By E. J. Mundell

NEW YORK, Nov 12 (Reuters Health) - Stem cells might someday be used as "seeds" for the harvest of transplantable brain cells that could slow or reverse Parkinson's disease, according to researchers in Sweden.

"Stem cells, for their ability to proliferate and differentiate into all possible cells in an individual, hold that therapeutic potential," explained researchers Goncalo Castelo-Branco and Dr. Ernest Arenas of the Karolinska Institute in Stockholm. Their findings were presented Sunday in San Diego, California at the annual meeting of the Society for Neuroscience.

Parkinson's disease is a chronic, progressively debilitating illness caused by the death of cells deep within the brain that produce dopamine, an important chemical that helps transmit nerve impulses. Preventing the loss of these dopamine-producing neurons, or replacing them once they are gone, is the "Holy Grail" of Parkinson's research.

Scientists have long known that the transplantation of neurons from fetal brain tissue into the brains of Parkinson's patients can help halt progression of the disease. But this technique is impractical since it "raises both technical and ethical problems," according to the researchers.

A solution would be to somehow direct stem cells to develop into dopamine-producing nerve cells in the laboratory, then harvest and transplant these cells into the brains of patients who need them. But just what conditions are necessary to transform stem cells into this highly specialized type of cell?

"This is precisely the key question that we are trying to solve," Castelo-Branco and Arenas told Reuters Health. The Swedish team has engineered embryonic stem cells to express a protein called Nurr 1. Nurr 1 acts as a kind of chemical "antenna," helping the stem cell pick up signals from other brain cells that would instruct it to develop into a dopamine-producing neuron. Identifying the exact source of that signal is the next stage in the investigators' research.

"In the future we hope to be able to identify the molecule(s) involved and then induce (the growth of) as many midbrain dopamine-producing neurons as we want," the researchers explained. The result, ideally, would be laboratory-based brain cell "farms"--a limitless source of transplantable neurons.

The procedure already appears to be working in mice, according to the study team, who say they have also been successful in "increasing the efficiency" of the technique in stem cells sourced from human embryos.

Much more research needs to be done, however, and the therapeutic use of laboratory-grown brain cells for Parkinson's patients is still years away. But Castelo-Branco and Arenas are optimistic that the technique might someday be used to treat other brain diseases, as well.

Huntington's disease--an inherited, degenerative neurological disorder--is one likely candidate, they say, because the disease "affects a defined population of neurons." Any effective treatment for this fatal illness "would be very important," the researchers conclude.

In a related study, researchers at Thomas Jefferson University in Philadelphia, Pennsylvania, say they have successfully directed stem cells from human bone marrow to grow into brain cells under laboratory conditions.

In a statement, lead researcher Dr. Lorraine Iacovitti said her team has "identified factors that get 100% of adult human bone marrow cells converted to neurons very quickly," although they have not yet been able to create brain cells capable of producing dopamine.

Another problem remains: All of the new neurons appear to revert back to undifferentiated stem cells within a few days. "The bigger problem to solve is how to keep them differentiated," Iacovitti said.

But she believes the findings hold great promise for Parkinson's patients. "The major advantage of using adult human bone marrow stem cells is that each person can be his own donor," she pointed out.
 

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