Apr. 9, 2001 DALLAS, April 6 – For the first time researchers have used bone marrow cells to reduce stroke-induced disability in rat experiments, according to a report in the April issue of Stroke: Journal of the American Heart Association.
The study showed that intravenous treatment with adult donor rat stromal cells (mature cells from bone marrow) allowed the rats to return to normal or near normal function within 14 days of a stroke.
“These are smart cells that selectively migrate to the site of injury and become little factories producing an array of helpful molecules to repair the tissue,” says Michael Chopp, Ph.D., professor and vice chairman of neurology at Henry Ford Health Sciences Center in Detroit, and professor of physics at Oakland University in Rochester, Michigan. “The beauty of this is that a patient could get multiple infusions.
“This study suggests that an infusion of the patient’s own stromal cells provides significant benefit to the stroke patient and are easily administered,” he says. “We believe we have a therapy that shows promise in treating stroke, Parkinson’s disease, spinal cord injury and traumatic brain injury.”
The treatment provides hope for the 600,000 people who have strokes in this country annually. Stroke remains the third leading cause of death, and a leading cause of disability.
The approach involves removing stromal cells, growing them in culture, and then infusing them back into the rat where they migrate to the site of injury - in this case the brain. Because the cells are taken from the same rat, the problem of rejection is eliminated. In previous studies of stromal cell treatment, the cells were either injected or surgically administered. This method eliminates the need for surgery and also allows for repeat treatments.
In the study, researchers tagged stromal cells with a chemical marker for tracking before re-infusing them. Cerebral strokes were induced in the rats and they were treated with a single dose of stromal cells at day one or day seven. Another group not treated with stromal cells served as controls.
The rats were given neurological, motor skill and sensory function tests before the stroke and at day one, one week and up to 35 days after the stroke. In general, the subjects treated with high dose infusions of stromal cells scored significantly better on the tests.
Additionally, biopsies revealed that the majority of the stromal cells migrated to the site of brain injury. Other cells were found around the vessels of major organs, but not within the organs, and in the bone marrow and the spleen.
Both rats treated at day one and day seven after stroke had similar recoveries. This is important, Chopp says, because it provides physicians with a time window for treatment. Some stroke patients are very unstable for the first day or two after stroke and the physicians may be reluctant to take bone marrow during this time period. Also, some patients with transient ischemic attacks (TIAs) or “mini strokes” – temporary stroke-like events caused by a temporarily-blocked blood vessel - spontaneously get better on their own.
“We found that you could wait at least seven days and get significant benefit,” notes Chopp. It is not yet clear how the procedure works. One theory is that stromal cells integrate into tissue and replace damaged cells. But more likely, Chopp believes, stromal cells may stimulate brain cells to repair themselves.
If the treatment continues to show beneficial effects in animal studies, it may provide new treatments in the future for stroke, brain trauma, spinal cord injury, and neurological diseases such as Parkinson’s disease, multiple sclerosis and even Alzheimer’s.
The researchers are applying to the National Institutes of Health for a grant for Phase I studies in humans.
Other researchers involved in this study include Jieli Chen, M.D.; Yi Li, M.D.; Lei Wang, M.D.; Zhengang Zhang, M.D.,Ph.D.; Dunyue Lu, M.D.; and Mei Lu, Ph.D.
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