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Stem cells act through multiple mechanisms to benefit mice with neurodegenerative disease

ne that makes the housekeeping enzyme hexosaminidase ("hex") deficient and, therefore, has Sandhoff's Disease, a lethal genetic disease related to Tay-Sachs Disease. When stem cells were implanted -- at simply one time point -- into brains of newborn Sandhoff mice, the onset of symptoms was delayed, well-being and motor function was preserved, and lifespan was extended by >70%.

The researchers discovered that their implanted neural stem cells, which migrated and integrated extensively throughout the brain, did much more than replace brain tissue destroyed by the disease. Some of the transplanted cells replaced damaged nerve cells and transmitted nerve impulses, offering the first evidence that stem cell-derived nerve cells may integrate electrically and functionally into a diseased brain. The transplanted cells also boosted the brain's supply of the enzyme Hex, which reduced the lipid accumulations in the treated animals. The experimental treatment also dampened the inflammation that typically occurs in the brains of most degenerative diseases, including Sandhoff's, and likely contributes to disease progression.

"Our studies suggest that functional neuronal replacement can be complemented and, under some conditions, eclipsed by a range of other stem cell actions that nevertheless exert a number of critical stabilizing forces," said Dr. Snyder, director of Stem Cells and Regeneration at Burnham. "In fact, our study offers the first evidence that stem cells employ multiple mechanisms -- not just cell replacement - which collaborate to benefit disease. These findings also raise the possibility - somewhat counter-intuitively -- that stem cells may inherently exert an anti-inflammatory influence in degenerative diseases," said Snyder.

To demonstrate that a better understanding of the fundamental mechanisms of stem cell action may permit the development of rational combined synergistic therapies, the investigators then gave
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Source:Burnham Institute


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