STANFORD, Calif. - A stroke leaves a permanent gap in the brain that can destroy a person's ability to speak and move normally. Filling that gap with new cells has been a long sought-after goal of stem cell research, but all attempts have met with complications - until now. Researchers at Stanford University School of Medicine report the first success using stem cells to populate the damaged region with new neurons in rats. If those cells also replace the function of the lost cells, they could help people recover after a stroke.
In the study, published in the July 26 advance online issue of Proceedings of the National Academies of Science, neurosurgeon Gary Steinberg, MD, PhD, and his group found that fetal stem cells injected into the brains of rats could migrate to the right location and turn into the appropriate types of neurons. "We're not saying we can treat patients immediately, but it's a big step forward. This gives us considerable optimism for these cells," Steinberg said.
The cells in question are at an early stage of developing into the mature brain and are still able to form many types of brain cells, but until now the cells have shown that potential only in a lab dish. Stem Cells Inc., a company founded by study co-author and pathology professor Irving Weissman, MD, reported isolating these cells from human fetal tissue in December 2000. The company now grows the cells in bulk and distributes them to researchers studying spinal cord injuries as well as Parkinson's, Alzheimer's and other brain disorders. Steinberg's is the first paper to show that the cells can transform into the appropriate cell types in an animal.
Steinberg said the fetal cells, called neurospheres, have advantages over both adult and embryonic stem cells for treating stroke. Adult brain stem cells produce new neurons throughout a person's life. After a stroke, these cells seem to repair some damage but aren't able to completely compensate for the lost tissue. In animal experiments, Steinberg's group has found that additional adult neuronal stem cells injected into the brains of rats may not survive long or migrate to the correct location.
Human embryonic stem cells have a different set of problems. Although embryonic stem cells show promise for treating rats with strokes, the human cells aren't widely available for research due to federal restrictions and aren't approved for use in humans. Even if the cells effectively treated stroke damage in rats, Steinberg couldn't offer that treatment to patients.
Fetal cells share the benefits of adult and embryonic cells without the drawbacks. This early study suggests that they will be more effective at treating stroke than adult cells. The cells are also available for research and are grown according to FDA-regulated Good Manufacturing Practice standards, unlike their human embryonic counterparts. This means the cells have already passed one FDA hurdle and could move to clinical trials in humans if Steinberg's follow-up experiments are successful.
Steinberg warns that this study did not look at whether fetal neurospheres helped rats recover brain function after a stroke. Instead, he and co-first authors Tonya Bliss, PhD, a research associate, and Steven Kelly, PhD, now at the University of Bristol, wanted to determine whether the cells migrated to the right place and turned into the right kind of cell. When stem cells were injected close to the site of the induced stroke, the cells survived in only one out of nine mice. Steinberg said this makes sense because the stroke site doesn't have a blood supply to keep the cells alive.
However, when injected a few millimeters away, the cells survived and migrated as far as 1.2 millimeters toward the stroke region. Steinberg believes signals from the damaged cells act as a distress call beckoning the transplanted cells. Other signals direct the newly arrived cells to transform into neurons and support cells called astrocytes. In rats without an induced stroke, the injected cells migrated only an average of 0.2 millimeters.
"The next step is to show recovery," Steinberg said. His group examined the transplanted cells after only four weeks, too soon to know whether the cells can help the rats recover. In the next set of experiments they will study whether the neurospheres help the rats recover normal movement after the stroke.
Michael Marks, MD, associate professor of radiology and a faculty member at the Stanford Stroke Center, said he is encouraged by Steinberg's findings. Marks said there is currently no way to treat patients who have lost brain function after a stroke. "This would be a very important therapeutic tool for us to have," he said, adding that existing treatments are only effective in the first few hours after the stroke. Most patients don't arrive at the hospital within that window and therefore have no options for reducing damage to their brain cells. "A therapy like this has tremendous potential," he said.
Every 45 seconds an American has a stroke, for a total of about 700,000 strokes per year. It is the leading cause of serious, long-term disability in the United States. Most strokes are caused by blood clots blocking vessels in the brain, cutting off the supply of oxygen and nutrients to brain cells. The remaining 12 percent of strokes occur when blood vessels burst and leak blood into the brain. Strokes are the third most common cause of death after heart disease and cancer.
Additional Stanford researchers involved in this study are technician Guo Hua Sun; undergraduates M. Ma and Wen-Chi Foo; Midori Yenari, MD, associate professor of neurosurgery and neurology; and Theo Palmer, PhD, assistant professor of neurosurgery.
Stanford University Medical Center integrates research, medical education and patient care at its three institutions - Stanford University School of Medicine, Stanford Hospital & Clinics and Lucile Packard Children's Hospital at Stanford. For more information, please visit the Web site of the medical center's Office of Communication & Public Affairs at http://mednews.stanford.edu.
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