More MS news articles for Nov 2001

Donor brain stem cells do more than just grow

Sunday Nov 11th, 2001
Investigators: Evan Snyder and Jeffrey Kocsis
by Apoorva Mandavilli

Neural stem cells (NSCs) can alleviate neural degeneration by instructing host cells to regenerate, rather than by maturing into neurons themselves, Harvard neurologist Evan Snyder said today. In mice with Purkinje cell (PC) degeneration, Snyder reports, NSCs may be reconstituting the PC layer either by protecting host cells or by stimulating a more vigorous regenerative response.

"We think this may be the donor cells secreting things that change the host," Snyder said. "And this may apply not just to NSCs but to many other types [of stem cells]." In fact, he suggests, the new model may explain some functional results now observed in other stem cell experiments.

Snyder and his colleagues transplanted donor NSCs into the cerebella of nervous (nr), Purkinje-cell-deficient (pcd), and lurcher (lc) mice with rapid degeneration of PCs. Transplanted NSCs dispersed broadly, but only a minority of them matured into neurons and glial cells, the researchers say.

But when transplanted at early stages of PC degeneration, NSCs nevertheless protected the cells from spontaneous degeneration. When grafted into newborn mice, the NSCs also preserved cerebellar architecture in both PC and granule cell populations. In such mice, motor deficiencies were reduced or absent, the scientists report.

The NSCs protect mice by interacting with host brain neuroprogenitor cells, either by stimulating their regenerative behavior or by protecting host cells from neural damage through trophic interactions, Snyder says. The mechanism may allow for treatment with a smaller number of stem cells, which might be safer.

Synder says he will now focus on molecular mechanisms responsible for the protection. But even if researchers completely identify the protective mechanism and its components, transplanting stem cells may still be the safest way to deliver the milieu for regeneration, Snyder says.

"The mutants are classic models of neural development and neural disease," said Ronald McKay of the US National Institute of Neurological Disorders and Stroke. "If he puts his cell line into lurcher, it rescues the lurcher defect. That's very nice."

McKay cautions against extrapolating the mechanism beyond Snyder's experiments, however. Stem cells may not always protect simply by communicating with host cells, McKay told BioMedNet News, adding that in many cases, "there is clear evidence that donor cells are regenerating."

One such example comes from neuroscientist Jeffrey Kocsis and his colleagues at Yale and Sapporo Medical University in Japan. Intravenous introduction of an acutely isolated rat bone-marrow cell fraction can enter the spinal cord and remyelinate axons, Kocsis reported today.

When the researchers injected millions of cells into a rat model of demyelination, which occurs in diseases such as multiple sclerosis, "there was massive repair," Kocsis said. "I say that not hyperbolically. There was massive repair."

In a second study, the researchers also injected bone-marrow-derived stem cells, called mesenchymal stem cells, into a rat model of demyelinating disease. Three weeks later, they found that the demyelinated axons were extensively repaired.

Such techniques, now being tested to repair cells in the liver and the heart, are very exciting because the bone marrow cells are "doing something they don't normally do," McKay said. The results may even suggest that bone marrow cells traditionally have a role to play in such repair, he notes.

"Bone marrow to blood, that's banal," he said. "But bone marrow into liver, into heart, into brain - that's cool."

SFN 2001 - Society for Neuroscience

Editor's Choice Links

Neurons from stem cells: implications for understanding nervous system development and repair.
Mansergh FCWride MARancourt DE
Biochem Cell Biol 2000 78:5 613-28

See also:

Developmental mechanisms in the pathogenesis of neurodegenerative diseases
Mark F. Mehler and Solen Gokhan
Progress in Neurobiology, 2001, 63:3:337-363

Stem cells and aging: expanding the possibilities [Review]
Mahendra S. Rao and Mark P. Mattson
Mechanisms of Ageing and Development, 2001, 122:7:713 - 734

Neural stem cells [Review]
Jack Price and Brenda P. Williams
Current Opinion in Neurobiology, 2001, 11:5:564-567

© Elsevier Science Limited 2000