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Exploring what's possible

University team harnesses the power of stem cells to repair the brain and spinal cord

Stem cell research by University of Minnesota neurosurgeon Ann Parr, M.D., Ph.D., offers hope that nerve damage caused by devastating spinal cord injuries may one day be repairable. (Photo: Scott Streble)

For years, doctors treating patients who had brain or spinal cord injury faced a terrible impasse.

“It was always considered impossible to regenerate damaged brain or spinal cells,” says University of Minnesota assistant professor and neurosurgeon Ann Parr, M.D., Ph.D.

For a person who had been in an accident or suffered a stroke, crushed neurons or blood-deprived brain tissue meant uncertain recovery and the possibility that loss of function, like walking or speaking, would be permanent.

But the thinking about brain injury has begun to change, in particular with the latest advances in stem cell research. Today’s stem cell technologies involve a wide range of naturally occurring and engineered cells, and they’re altering the outlook on restoring the highly specialized brain and spinal cord.

In the Medical School’s Department of Neurosurgery, a new group of researchers is focused on stem cells and how their astounding capabilities may be harnessed to help patients regain function.

Walter Low, Ph.D., is studying how stem cells can minimize long-term damage caused by a stroke.

Scientist Walter Low, Ph.D., the department’s associate head for research, has long been interested in how stem cells might minimize brain damage following a stroke. His research involves using stem cells that exist in umbilical cord blood from the placentas of newborn babies to help repair the brain after an injury.

Low’s group found that a subset of stem cells from cord blood is capable of differentiating into precursors of neural cells in the brain. He was amazed by how the cells repaired brain tissue in animal models.

“We’ve found that if we give stem cells two days after a stroke, we can reduce the infarct volume by 50 percent,” he says. (An infarct is a lesion left behind in the brain after it’s been deprived of blood and oxygen.)

That’s a tremendous opportunity, he points out. A typical emergency room treatment for stroke is the clot-busting drug tPA, which can restore blood flow to brain tissue if it’s given within just three to four hours of a stroke.

A stem cell therapy may increase the window in which treatment can be given.

Low says these cells seem not only to regenerate neural cells, but also to have a protective effect on the vulnerable area of the brain around the site of the stroke.

“We could conceivably preserve a lot of brain tissue with the administration of these cells,” he says.

Low’s next steps involve validating the research findings and beginning to work out parameters to determine, for example, how many stem cells might be needed to be an effective therapy for a person who’s had a stroke.

“Ultimately,” he says, “we’d like to scale up for a clinical trial.”

Reprogramming cells

Neurosurgeon Parr became interested in the potential of stem cells as she treated patients who had suffered life-altering spinal cord injuries.

“They’re very often young people,” she says, “and their lives have been turned inside out.”

In studies of rats with spinal injuries, she found that an infusion of neural stem cells, those capable of becoming brain cells, could restore motor function. Most of those stem cells turned into one specific type of neural cell called oligodendrocytes, which produce the insulating, fatty myelin sheath that protects the nerves.

It’s not clear yet whether the stem cells protect damaged nerves from toxins or provide new insulation for the nerves, Parr says. The cells may even offer a healthy surface for regrowing nerves, she says.

The cells’ beneficial effect prompted Parr’s upcoming research. She is developing the technology to produce oligodendrocyte progenitor cells, cellular precursors to the mature oligodendrocytes, which potentially can be used as therapy. Her research involves taking a patient’s own skin cells, called fibroblasts, and genetically converting them back into stem cells, in essence “turning off” their former genetic identity, Parr says. Then she’ll steer the cells to develop into oligodendrocyte progenitor cells.

“Brain and spinal cord injuries are so devastating to patients, and there’s very little we can offer them,” Parr says. “Our goal with all of these studies is to bring treatments to the clinic where they may provide patients with new hope.”

Andrew Grande, M.D., and his lab team are investigating new ways to deliever stem cell therapies to the brain during surgery. (Photo: Richard Anderson)

Redirecting the body’s own cells

Another line of research by endovascular neurosurgeon Andrew Grande, M.D., is addressing the best way to access those potentially life-changing neural stem cells that are found in certain areas of the brain.

Grande is investigating using a microcatheter threaded into the brain to steer naturally occurring neural stem cells from areas known as the subventricular zone and the hippocampus to the area where a stroke has occurred.

“There’s a constantly replenishing source of neurogenerating stem cells in these areas, and the body knows what to do with them,” says Grande, who joined the University in September after receiving the prestigious William P. Van Wagenen Fellowship, an award for a top resident pursuing academic medicine. “The question is, can we somehow lasso this capability and direct these cells elsewhere to produce new neurons in an area of injury?”

The microcatheter may be useful in a range of stem cell therapy techniques, Grande says. He currently uses microcatheters to diagnose stroke and to deliver clot-busting drugs in tiny blood vessels. But he’s interested in developing new ways to deliver stem cell therapies to the brain during neurosurgery.

“With my particular clinical background,” he says, “this is something unique I hope to bring to stem cell therapy.”

Where doctors have had little help to offer people with brain injuries, the horizon is growing brighter. Parr notes that scientists need to pursue these research avenues with great care, looking for adverse effects and possible complications before these advances can move to human clinical trials.

“Patients ask me, how close are we to discovering treatments? I think we’re getting close,” she says. “In the next few years there will be some treatments, especially for patients whose spinal injuries are new. This field is moving very quickly.”

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