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Human Stem Cells Used to Treat Nerve Disease in Mice

by Rajshri on Jun 6 2008 3:18 PM

Human stem cells have been used by researchers at the University of Rochester Medical Center to treat a fatal nerve disease in mice that displays the same characteristics as several conditions seen in children.

The team said that this achievement might now help researchers in developing new strategies for treating certain hereditary and perinatal neurological disorders.

In this study, the researchers were able to restore the absent or lost myelination to diseased nerve fibers in the 'shiverer mouse' animal model, which lacks normal myelin and typically dies within months of birth.

Normally, nerve cell projections are ensheathed by a fatty substance called myelin that is produced by oligodendrocytes, a type non-nerve cell in the brain and spinal cord. Myelin enhances the speed and coordination of the electrical signals by which nerve cells communicate with one another. When myelin is missing or damaged, electrical signals are not properly transmitted.

Thousands of children with rare, fatal disorders known as paediatric leukodystrophies share a central problem with the shiverer mice: Their brain cells lack sufficient myelin.

While earlier studies have tried cell transplantation to treat these diseases, but till date no transplantation of human neural stem cells or of their derivatives, called glial progenitor cells, have ever altered the condition or fate of recipient animals.

But now researchers led by Dr. Steve Goldman from the Departments of Neurology and Neurosurgery at the University of Rochester Medical Center, along with collaborators at Cornell, UCLA and Baylor, built their study on earlier work by devising a more robust method for the acquisition and purification of human fetal glial progenitor cells.

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Besides, they also developed a new cell delivery strategy, based on multiple injection sites, to encourage widespread and dense donor cell engraftment throughout the central nervous system of recipient mice.

They succeeded in transplanting human glial stem cells into neonatal shiverer mice that also had a genetically deficient immune system. They used immunodeficient mice to minimize the rejection of the transplanted cells.

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It was discovered that the new transplant procedure resulted in infiltration of human glial progenitor cells throughout the brain and spinal cord. The engrafted mice displayed robust, efficient and functional myelination. Particularly, many of the mice exhibited progressive, neurological improvement and a fraction of the mice were actually rescued by the procedure.

"The neurological recovery and survival of the mice receiving transplants was in sharp contrast to the fate of their untreated controls, which uniformly died by five months," explained Goldman.

It was found that the histological examination continuing over a year after the procedure showed that the white matter of the surviving mice had been essentially re-myelinated by human cells.

"To our knowledge, these data represent the first outright rescue of a congenital hypomyelinating disorder by means of stem or progenitor cell transplantation. Although much work needs to be done to maximize the number of individuals that respond to transplantation, I think that these findings hold great promise for the potential of stem cell-based treatment in a wide range of hereditary and ischemic myelin disorders in both children and adults," said Goldman.

The study is published by Cell Press in the latest issue of the journal Cell Stem Cell.

Source-ANI
RAS/L


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