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Pitt surgeons transplant brain cells in attempt to repair stroke damage

Wednesday, July 01, 1998

By Byron Spice, Science Editor, Post-Gazette

Surgeons at the UPMC Health System have transplanted brain cells into a patient in what the university contends is the world's first attempt to repair brain damage from a stroke.

Details of last week's procedure are to be released at an 11 a.m. news conference today.

Though a number of researchers have used fetal cell implants to treat patients with Parkinson's disease, the Pitt procedure involved the use of engineered human neurons, or brain cells.

"It's an interesting and very promising area," said Dr. Chung Y. Hsu, head of the Cerebrovascular Disease Center at Washington University School of Medicine in St. Louis. But repairing stroke damage is likely to be far more difficult than treating Parkinson's or even repairing spinal cord injuries, he warned.

Stroke treatment in recent years has focused on halting strokes as they occur or preventing damage to brain cells in the hours after a stroke occurs. Afterward, rehabilitation has been the only option. Doctors have never been able to repair brain cell damage once it occurs.

"This study, if it proves successful, will be the first thing that can help people post-stroke, anywhere from six months to perhaps two years afterward," said Rachelle Trujillo, spokeswoman for the Colorado-based National Stroke Association.

Stroke is the third leading cause of death and the leading cause of serious long-term disability in the United States.

"We're talking about more than 3 million disabled stroke victims in this country alone," Hsu said.

A stroke, or brain attack, occurs when the brain's blood supply is interrupted, either by a blockage in an artery or a sudden bleed. Brain cells die when deprived of the oxygen in blood. The body cannot replace a dead brain cell.

The Pitt doctors used cells developed in the laboratory of Virginia M.-Y. Lee, a neurobiologist at the University of Pennsylvania. Rather than use fetal cells, Lee and her colleagues took a mixture of cells from a human cancer tumor. The mixture included immature, "progenitor cells," -- cells that have not "differentiated" to become a particular kind of cell.

The Penn researchers use retinoic acid to make the progenitor cells non-cancerous and to push them to develop into brain cells, or neurons.

Lee and collaborators from the University of South Florida reported in February in the journal Experimental Neurology that infusions of the engineered neurons had restored brain function in rats who had artificially induced strokes.

The cell line, which has been patented by Penn, would sidestep the controversy involving the use of fetal cells, Trujillo said. The federal government banned the use of human fetal tissue for research until 1994, when the ban was lifted under President Clinton.

Researchers increasingly have tried to move away from fetal cells to some sort of genetically engineered tissue, Hsu said. Ideally, a person's own skin cells might be removed, genetically reprogrammed to produce a desired brain chemical, and then implanted in the brain.

Use of fetal cells in Parkinson's patients has had mixed results to date, he said. To treat Parkinson's, he said, doctors are interested only in transplanting dopamine-producing cells, replacing the dopamine-producing cells that selectively die off in these patients.

Repairing spinal cord injuries would be a step higher in difficulty, Hsu said. In that case, doctors are trying to reconnect severed nerves. But clinical trials have been attempted only in Russia.

Stroke is a much more complex and difficult injury to repair because it involves many types of cells and brain functions, he said. Pitt researchers would be far ahead of other U.S. scientists if they are able to attempt such a repair.

"This is like putting a man on the moon," Hsu said, and probably will require many steps and revisions before it proves successful.



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