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Transplant of pig tissue may reduce stroke size and damage

02.09.2004


A tiny capsule containing tissue that secretes a cocktail of brain-nourishing neurotrophic factors may one day help reduce the damage and disability of stroke, according to research published in the September issue of Stroke.



Choroid plexus tissue has innate roles in developing and protecting the brain and when additional tissue is transplanted into an animal model of stroke, it reduces stroke size by about 65 percent, Medical College of Georgia researchers report. "What we have seen is the reduction of the size of the stroke in the brain, and the animals that received the transplant showed functional recovery in motor as well as neurological function," said Dr. Cesario V. Borlongan, MCG neuroscientist and first author on the paper.

The study is an important step in moving the potential treatment to clinical trials because the porcine choroid plexus tissue also could be used in humans, Dr. Borlongan said. The cells of the pig choroid plexus are similar in size and function to human cells and pig brain tissue has been used in humans to treat Parkinson’s disease.


For the study, researchers put the pig tissue into biocompatible microcapsules before transplanting them into the rat stroke model. To objectively assess its effectiveness, they compared the results to an empty capsule as well as choroid plexus tissue without the capsule and no treatment. "We have seen in this study that choroid plexus alone, without any capsule, also can reduce stroke damage," said Dr. Borlongan. But they also found increased inflammation when the capsules – designed by LCTBioPharma, Inc., in Providence, R.I., a subsidiary of Living Cell Technologies based in New Zealand and Australia – were not used.

The capsules are designed to allow molecules, such as protective neurotrophic factors, to escape and keep out inflammatory factors that could trigger an immune response and rejection. And they could one day hold more than choroid plexus. "There are different therapies we can combine with this encapsulated therapy, including other substances such as stem cells to help replace brain cells that are lost," Dr. Borlongan said. "We are excited about the potential therapeutic benefits of the choroid plexus but we are moving cautiously toward the idea of using this approach in humans."

Dr. Borlongan published a similar study showing the benefit of rat-to-rat transplants in the May 2004 issue of NeuroReport. He also presented the rat studies as well as early findings on the pig-to-rat transplant studies at the May meeting of the American Society for Neural Transplantation and Repair.

For the Stroke paper, he completed parallel studies in culture that showed brain cells exposed to media collected from the encapsulated choroid plexus survived oxygen deprivation. Now he’s looking long-term at how the encapsulated versus "naked" tissue is tolerated in his animal model. Non-human primate studies will be needed as well before human trials can begin.

One obvious challenge of turning the laboratory findings into an actual new therapy is that the reparative benefits of choroid plexus likely work best immediately after a stroke; right now the Food and Drug Administration typically doesn’t allow invasive procedures immediately after a stroke unless patients are hemorrhaging and need surgery to stop bleeding. The only FDA-approved drug therapy to date in the hours immediately following a stroke resulting from a blood clot is intravenous infusion of the clot-dissolving drug, TPA. Invasive procedures can be used only for chronic stroke, patients who are severely sick, debilitated and not responding, Dr. Borlongan says.

That means any clinical trials likely would start with these chronic patients, who may also benefit. "We want to show first that it’s safe and second that it’s feasible, that when you transplant these cells into a patient, they won’t be rejected and the patient won’t show any detrimental side effects," Dr. Borlongan says, estimating that such studies are likely two years away.

Toni Baker | EurekAlert!
Further information:
http://www.mcg.edu

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