Transplant cells show capacity for mending nervous system

July 29, 1999

MADISON - Using stem cells grown in the laboratory, scientists have successfully transplanted those cells into the nervous systems of ailing rats and arrested the course of a debilitating congenital disease.

Although accomplished in rats and still some years from clinical application, the work is important because it shows that cells grown from scratch can be used to repair defective nerves. The report was published this week (Friday, July 30) in the journal Science by a team of scientists from the University of Bonn Medical Center, the National Institute of Neurological Disorders and Stroke (NINDS) and the University of Wisconsin-Madison.

The work was accomplished using embryonic stem cells, ephemeral cells that arise within days of conception in a fertilized egg and very quickly develop into all the different kinds of cells -- blood, bone, muscle, neurons -- that make up the body. Such cells hold enormous therapeutic potential to treat disease through the promise of unlimited supplies of laboratory-grown replacement tissue to treat many congenital and acquired diseases, including heart disease, neurological disorders such as Parkinson's disease or multiple sclerosis, and other diseases such as diabetes.

In the new study, stem cells were coaxed down a developmental pathway to become oligodendrocytes and astrocytes, key cells of the central nervous system. Transplanted into the spinal cords of fetal and newborn rats that lack myelin, a tissue that covers some nerve fibers, the cells were observed to promote the growth of the myelin sheaths essential to the ability of nerves to conduct electrical impulses and function normally.

"This is the first study showing that embryonic stem cells can be used for brain and spinal cord repair in an animal model of a human neurological disease," said Oliver Brüstle, a neuropathologist at the University of Bonn and first author of the paper.

Ronald D.G. McKay, chief of the NINDS Laboratory of Molecular Biology and a co-author of the paper, said "the study shows that precursor cells with potential for cell therapy can be generated simply and efficiently from embryonic stem cells."

Two weeks after being surgically transplanted into either fetal or newborn rats with a congenital disease identical to the rare human myelin disorder Pelizaeus-Merzbacher disease, the laboratory-grown cells had developed into numerous myelin sheaths around nerve fibers previously without myelin. When the cells were transplanted into the fetal brain they were later found to have spread widely.

"Our findings demonstrate that cells that have never seen a brain can be developed into specific donor cells for nervous system repair," said Brüstle. Although the set of experiments did not show improved function as a result of the newly formed myelin, it is likely that repaired nerve fibers would conduct normally, said Ian Duncan a UW-Madison professor of neurology, a co-author of the Science paper and an authority on myelin deficiency diseases.

As a strategy for repairing damage by diseases such as multiple sclerosis, Duncan noted that this approach focuses on replacing lost myelin, not stopping ongoing disease, something that will require additional medical therapy. "Nonetheless we believe eventually it will have clinical applications," he said.

Myelin is a critical insulator, helping nerve fibers conduct the electrical impulses that drive ambulation, speech, sight and hearing. Without it, fibers conduct slowly or not at all. The absence of myelin is a manifestation of an array of dire genetic and acquired diseases, the best known being multiple sclerosis.

Importantly, in the study no teratomas -- tumors that frequently arise when undifferentiated stem cells are transplanted into animals -- were generated.

"In no instance did we see the formation of teratomas," said Duncan, "It strongly suggests they will not form under these circumstances, but this needs to be studied over a longer period of time."

In addition to Duncan, authors of the paper published today in Science include, Brüstle, and colleagues Kimberly N. Jones, Khalad Karram, Khalid Choudhary and Otmar D. Wiestler of the University of Bonn Medical Center; McKay of the NINDS; and Randall D. Learish of the University of Wisconsin-Madison.
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NOTE TO REPORTERS: Ian Duncan is on vacation this week but can be reached through Friday at 715-798-3423 or by e-mail.



University of Wisconsin-Madison

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