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Old 10-15-2006, 05:28 AM #1
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Default Human stem cells delay start of Lou Gehrig's disease in rats

Researchers at Johns Hopkins have shown that transplanting human stem cells into spinal cords of rats bred to duplicate Lou Gehrig's disease delays the start of nerve cell damage typical of the disease and slightly prolongs life. The grafted stem cells develop into nerve cells that make substantial connections with existing nerves and do not themselves succumb to Lou Gehrig's, also known as amyotrophic lateral sclerosis (ALS). The study is published in this week's issue of Transplantation.
"We were extremely surprised to see that the grafted stem cells were not negatively affected by the degenerating cells around them, as many feared introducing healthy cells into a diseased environment would only kill them," says Vassilis Koliatsos, M.D., an associate professor of pathology and neuroscience at Hopkins.
Although all the rats eventually died of ALS, Koliatsos believes his experiments offer "proof of principle" for stem cell grafts and that a more complete transplant of cells - already being planned -- along the full length of the spine to affect upper body nerves and muscles as well might lead to longer survival in the same rats.
"We only injected cells in the lower spine, affecting only the nerves and muscles below the waist," he noted. "The nerves and muscles above the waist, especially those in the chest responsible for breathing, were not helped by these transplanted stem cells."
The research team used so-called SOD-1 rats, animals engineered to carry a mutated human gene for an inherited form of ALS. As in human ALS, the rats experience slow nerve cell death where all the muscles in the body eventually become paralyzed. The particular SOD-1 rats in the study developed an "especially aggressive" form of the disease.
Adult rats not yet showing symptoms were injected in the lower spine with human neural stem cells - cells that can in theory become any type found in the nervous system. As a comparison, the researchers injected rats with dead human stem cells, which would not affect disease progression. Both groups of rats were treated with drugs to prevent transplant rejection.
The rats were weighed and tested for strength twice a week for 15 weeks. Weight loss, according to Koliatsos, indicates disease onset. On average, rats injected with live stem cells started losing weight at 59 days and lived for 86 days after injection, whereas control rats injected with dead stem cells started losing weight at 52 days and lived for 75 days after injection.
The rats were coaxed to crawl uphill on an angled plank, and their overall strength was calculated by considering the highest angle they could cling to for five seconds without sliding backwards. While all the rats grew progressively weaker, those injected with live cells did so much more slowly than those injected with dead cells.
Close examination of the transplanted cells also revealed that more than 70 percent of them developed into nerve cells, and many of those grew new endings connecting to other cells in the rat's spinal cord.
"These stem cells differentiate massively into neurons," says Koliatsos, "a pleasant surprise given that the spinal cord has long been considered an environment unfavorable to this type of transformation."
Another important feature of the transplanted cells is their ability to make nerve-cell-specific proteins and growth factors. The researchers measured five-times more of one particular factor, known as GNDF (short for glial cell derived neurotrophic factor) in spinal cord fluid. The transformation of the transplanted cells also may allow them to deliver these growth factors to other cells in the spinal cord through physical connections.
Cautioning that clinical applications are still far from possible, Koliatsos hopes to take further advantage of his rodents with ALS to learn as much as possible about how human stem cells behave when transplanted.



http://www.eurekalert.org/pub_releas...-hsc101006.php
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Old 10-15-2006, 09:29 PM #2
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Rob ,
Interesting article...thanks for posting this..I just hope it has as much promise as the press release indicates..it will be interesting to get Dr.McCarty's take on it...Lisa

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Old 10-16-2006, 07:45 AM #3
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Despite this experiment showing no life extension, I find it promising. Note that breathing was not targeted in the implantation. First the neurons formed well from cells with over 70% developing. Secondly, the neurons were not killed off by ALS suggesting that an eventual therapy will grow neurons faster than they die off. I suspect continued development of this approach will also reveal new aspects of the disease that may open other therapy approaches. Imagine where we would be now if Bush hadn't slammed the door on federal funding.
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Old 10-16-2006, 08:01 AM #4
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John...I appreciate your insight and fully agree with you on the funding isssue...
I've learned to be very leary of press releases though.,,
I have my doubts on stem cells being able to cure ALS alone..but do not want any avenue tht may benefit PALS slammed shut...my personal hope with stem cells is that they may be the key to restoring partial function once the disease itself has been arrrested....when meds to do that are found...Lisa

Last edited by lisag; 10-16-2006 at 08:07 AM.
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Old 10-16-2006, 09:33 AM #5
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http://news.bbc.co.uk/1/hi/health/6054572.stm
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Old 10-16-2006, 03:32 PM #6
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Hi guys..thought some of you might want to see the discussion going on at the TDF site about this...and Dr. McCarty's comments on this thread..
http://www.als.net/forum/topic.asp?TOPIC_ID=971
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