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Stem Cell Research Targets Diseases of the Central Nervous System

Researchers at the University of Missouri-Columbia have conducted experiments that might lead to stem-cell therapies for a variety of neurodegenerative diseases of the central nervous system, such as Alzheimer's and Parkinson's

May 23, 2003
University of Missouri-Columbia
Columbia, Mo.

Researchers at the University of Missouri-Columbia have successfully transplanted mouse embryonic stem cells into mouse models for human diseases of the central nervous system. This stem-cell therapy might prevent or delay the death of defective host cells, and the findings could lead to stem-cell therapies for a variety of neurodegenerative diseases of the central nervous system, such as Alzheimer's and Parkinson's. The work also could lead to new treatments for spinal-cord injury and stroke.

"One approach using stem-cell therapy is to deliver therapeutic agents that will prevent host nerve cells from dying," said Mark Kirk, professor of biological sciences at the University of Missouri-Columbia. "It's the loss of brain cells that leads to the neurodegenerative disease process. If you provide host cells with something that sustains them, you may be able to cure or at least delay the onset of the pathology."

Kirk and MU colleagues, including professors Joel Maruniak in biological sciences and Martin Katz in the department of ophthalmology, and graduate student Jason Meyer in biological sciences, transplanted the stem cells into mice that had genetic mutations predisposing them to Batten disease, a progressive disorder that leads to retinal degeneration. In humans, Batten disease eventually causes brain atrophy, seizures, cognitive decline and premature death. Before these latter, serious symptoms surface, however, the disease impairs a victim's vision. Although Batten disease is rare, the stem-cell therapy approach to treat it applies to other diseases of the central nervous system, Kirk said.

Kirk's research team injected the stem cells during the early stages of photoreceptor degeneration. The stem cells injected into the mouse eye expressed green fluorescent protein that enabled the scientists to track the donor cells. The researchers also added a special acid to direct their cells' developmental fate, said Kirk. This modification caused the donor cells to "neuralize," which means they develop the properties of neurons and glial cells, the cell types found in the retina and central nervous system. Most importantly, the defective host cells responded favorably to the treated stem cells, and synapses, or connections, appeared to be established between the host and donor cells.

The therapeutic effects of the stem cell integration revealed a restoration of photoreceptors, the parts of the eye that are responsible for sensing and receiving light. In other words, as Kirk explained, the donor cells acted upon the defective host cells to keep them from dying. The researchers also used an electroretinogram, a device that measures the response of the retina to light stimulation, on the mouse eye that received "neuralized" embryonic stem cells and found evidence that photoreceptors were spared from degeneration.

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