Stem Cells Fill Gap Left By stroke, Say Stanford Researchers
Public release date: 26-Jul-2004

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Mitzi Baker
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Stanford University Medical Center

Stem cells fill gap left by stroke, say Stanford researchers

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

SOURCE: EurekAlert, DC
http://www.eurekalert.org/pub_releases/2004-07/sumc-scf072204.php

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