November 07, 2002
Neural Stem Cells Induced To Make Dopamine

The neural stem cells in this study are adult stem cells that are present in the adult human brain. While this article doesn't state it they are probably from the hippocampus. These cells normally differentiate to create neurons to form new memories and to replace lost cells. In Parkinson's Disease there is a particular type of neuron that makes the neurotransmitter dopamine that dies at a much faster rate than normal. One potential way to treat Parkinson's is to induce the adult stem cells to reproduce at a faster rate and to differentiate into dopamine-producing neurons to replace the lost neurons. A research group at Jefferson Medical College has demonstrated that it is possible to induce human adult neural stem cells to produce dopamine:

Developmental biologist Lorraine Iacovitti, Ph.D., professor of neurology at Jefferson Medical College of Thomas Jefferson University in Philadelphia, is searching for ways to convert stem cells into dopamine-making neurons to replace those lost in Parkinson's. In previous work, she and her co-workers showed that mouse neural stem cells placed in rats with Parkinson's disease could develop into brain cells that produced tyrosine hydroxylase (TH), the enzyme needed to make dopamine.

Dr. Iacovitti, who also is associate director of the Farber Institute for Neurosciences at Jefferson, wanted to see if human neural stem cells could become dopamine-producing brain cells as well. She and her colleagues grew neural stem cells in a laboratory dish. Using a cocktail of protein growth factors and nutrients, the researchers found they could coax approximately 25 percent of the stem cells to make TH in the dish, proving the stem cells had the capacity to manufacture dopamine. What's more, when they removed the growth factor-cocktail, the cells continued to produce the enzyme. She reports her team's findings November 5 at the annual meeting of the Society for Neuroscience in Orlando.

"We have two examples of human stem cells that do this," she says. "The obvious extension [of these results] is to take those predifferentiated human dopamine neurons and transplant then into Parkinson's disease model systems."

This is still a long way away from a useful therapy. But the value of this result is that it shows that the neural stem cells have the potential to produce dopamine. They haven't gone down a differentiation path that precludes their ability to make dopamine. This is great news.

Using adult stem cells to do this has a few advantages aside from the obvious one of avoiding the ethical objections some people have to the use of embryonic stem cells. First of all, it is theorized by some scientists that adult stem cells may be at lesser risk of converting into cancer cells than embryonic stem cells. Also, neural stem cells, being more differentiated than embryonic stem cells, are some unknown number of steps closer to being neurons. So to convert them to neurons of a particular type may turn out to be easier to do. Adult stem cells are also already immunologically compatible with their hosts. Another big potential advantage is that adult stem cells are already in the host body. It may be possible to come up with a mix of drugs and/or gene therapy that would flow up into the brain and tell those adult neural stem cells to reproduce at a much faster rate and convert into dopamine-producing neurons.

The ability to better control adult neural stem cells has other applications in treatment of disease. See this recent post on hippocampal stem cells and depression for another example. In the long run the ability to do gene therapy on adult neural stem cells and to control their cell division and differentiation will be useful not only for treating classical neurological disorders such as Parkinson's but also to rejuvenate aging brains, to help lift depression, to repair traumas to the brain, and even to raise intelligence.

Share |      Randall Parker, 2002 November 07 11:29 AM  Biological Mind

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