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Clinical and Research News
Stem Cells May Hold Key To Treating Brain Disorders
Psychiatric News
Volume 38 Number 6 page 32-50

The therapeutic use of stem cells, already promising radical new treatments for cancer, immune-related diseases, and other medical conditions, may someday be extended to repairing and replenishing the brain.

Stunning new research, still in its early stages, suggests that stem cells—the primitive "starter" cells found in bone marrow that have attracted the attention of researchers worldwide for their regenerative capacities—could offer breakthrough therapies for stroke, brain injury, Parkinson’s disease, Alzheimer’s disease, and other neurodegenerative conditions.

Much of the research on how stem cells might work to repair or replenish the brain has been in animals. But now, scientists at the National Institutes of Health (NIH) have shown that adult human bone-marrow cells can enter the brains of human transplant recipients—and that those cells will generate new neurons in the brain.

"This is an example of how the whole field of stem-cell plasticity is really exploding," said Eva Mezey, M.D., Ph.D., lead researcher on the study. She is head of the in-situ hybridization facility at the National Institute of Neurological Diseases and Stroke at the NIH. "I think it can give a completely new direction to medicine, adding to presently available treatments all kinds of new cell therapies, not only for the brain but all over the body."

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Mezey and her colleagues examined postmortem brain samples from four female patients with leukemia or immune-related diseases who had received bone-marrow transplants from male relatives. The strategy of looking at cross-gender transplant recipients provided the researchers a ready-made way to determine whether transplanted stem cells had migrated to the brain: any such cells would invariably carry a Y chromosome.

True to their hypothesis, sophisticated cell-staining technology showed that all four patients had Y-positive cells in their brain samples.

Most of these cells were not neurons, Mezey noted. But some of them were, indicating that the stem cells had not only migrated to the brain, but had "differentiated"—assuming the function of their surroundings, precisely as they have been found to do in other parts of the body.

Interestingly, most of the migrated stem cells were in the hippocampus. "The hippocampus is involved in memory management," she said. "One can imagine that in an area of the brain where new connections are being made all the time, new cells will be needed all the time."

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So, she said, something in the function of the brain is "recruiting" transplanted stem cells from the bloodstream to an area in the brain where they are needed most. That finding complements animal studies showing that transplanted stem cells migrate to—and differentiate into the form and function of—surrounding cells in brain areas that are damaged.

Uncovering that function is a challenge for the future.

"If we know the factors that recruit stem cells from the circulation, one can imagine injecting those factors into the site of a lesion—say, from a stroke—and increasing the number of circulating stem cells," Mezey said. Mezey’s findings appear to be the first human evidence of the migration and differentiation of transplanted stem cells in the brain, adding to a large and growing body of animal and laboratory research.

But she and other scientists in the field note that one of the most important revelations to emerge from a decade of research in this area is that the brain itself—in addition to recruiting transplanted stem cells from the bloodstream—appears to be continually producing its own stem cells, and repairing and replenishing itself.

Darwin J. Prockop, M.D., director of the center for gene therapy at Tulane University School of Medicine in New Orleans, noted that the finding overturns a long-held belief that the brain houses a finite number of cells that are lost irrevocably when they die.

Yet it appears that the brain’s natural production of stem cells occurs far too slowly, generating too few cells to repair the damage that typically occurs in the case of a stroke, spinal-cord injury, or neurodegenerative disease.

A key, then, to realizing the therapeutic potential of stem cells in the brain is increasing the volume of their production, Prockop explained. In contrast to Mezey, who looked at whole stem cells (which were typically used at the time when the patients in her study had been transplanted), Prockop and colleagues have studied specialized cells within bone marrow known as marrow stromal cells (MSCs). MSCs appear to have remarkable regenerative capacities, stimulating the growth of new cells anywhere in the body. More importantly, Prockop and colleagues have shown that MSCs can be extracted from bone marrow and grown in the laboratory rapidly and in enormous numbers.

"You can grow them in culture and make billions of them," he explained.

By injecting the multiplied MSCs into the site of a lesion, Prockop and his colleagues hope to enhance the brain’s natural production of stem cells and thereby enhance repair and restoration of function—a vision that has been realized in animal studies.

In a study published in the February 19, 2002, Proceedings of the National Academy of Sciences, researchers in Prockop’s laboratory exposed the spinal cord of a rat to injury, paralyzing the animal’s hind limbs and lower body. MSCs, grown in exponential numbers in the laboratory, were then injected into the site of the injury. "One week after the injury, motor function improved dramatically," Prockop told Psychiatric News.

The regulatory and scientific hurdles to be overcome are many before stem cell therapy will be a reality, but scientists are enthusiastic. Prockop believes the most likely first use of stem-cell therapy will be to repair spinal-cord injury.

And he does not rule out the potential for treating Alzheimer’s, Parkinson’s, and other neurodegenerative diseases. In the most visionary formulation of the new field, some scientists have spoken of using stem cells as a veritable "fountain of youth" for the brain.

Providing psychiatrists an overview of the new science during the 2001 APA annual meeting in New Orleans, Prockop underscored the stunning nature of the possibilities inherent in the field.

"I cannot prove that we can use the marrow as the equivalent of a fountain of youth, but we are moving close to that possibility," he stated at the meeting. "Now is the time for us to seriously debate it and discuss the consequences of where the science is moving. We need to discuss this not only among scientists but also among physicians and the lay public." ▪

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