Human Stem Cells Aid Stroke Recovery In Rats
ScienceDaily (Feb. 19, 2008) — Neural cells derived from human
embryonic stem cells helped repair stroke-related damage in the
brains of rats and led to improvements in their physical abilities
after a stroke, according to a new study by researchers at the
Stanford University School of Medicine.
This study marks the first time researchers have used human embryonic
stem cells to generate neural cells that grow well in the lab,
improve a rat's physical abilities and consistently don't form tumors
when transplanted.
Though the authors caution that the study is small and that more work
is needed to determine whether a similar approach would work in
humans, they said they believe it shows the potential for using stem
cell therapies in treating strokes.
Senior author Gary Steinberg, MD, PhD, the Bernard and Ronni Lacroute-
William Randolph Hearst Professor of Neurosurgery and the
Neurosciences, said that with 750,000 people having strokes in the
United States each year, the disease creates a massive burden for
stroke victims, their families and the medical system.
"Human embryonic stem cell-based therapies have the potential to help
treat this complex disease," Steinberg said, adding that he hopes the
cells from this study can be used in human stroke trials within five
years.
Human embryonic stem cells are able to form any cell type in the
body. Pushing those cells to form neural stem cells rather than other
types of cells has been a substantial hurdle, as has avoiding the
cells' tendency to form tumors when transplanted. Because embryonic
stem cells are still immature and retain the ability to renew
themselves and produce all tissue types, they tend to grow
uncontrollably into tumors consisting of a mass of different cells.
First author Marcel Daadi, PhD, a senior scientist in Steinberg's
lab, said the team overcame those obstacles by growing the embryonic
stem cells in a combination of growth hormones that nudged the cells
to mature into stable neural stem cells. After six months in a lab
dish, those neural stem cells continued to form only the three
families of neural cells—neurons, astrocytes and oligodendrocytes—
no tumors.
Convinced that the cells appeared safe, Daadi and co-author Anne-Lise
Maag, a former research assistant, transplanted those cells into the
brains of 10 rats with an induced form of stroke. At the end of two
months, the cells had migrated to the damaged brain region and
incorporated into the surrounding tissue. None of those transplanted
cells formed tumors.
Once in place, the transplanted cells helped repair damage from the
induced stroke. The researchers mimicked a stroke in a region of the
brain that left one forelimb weak. This model parallels the kinds of
difficulties people experience after a stroke.
Testing at four weeks and again at eight weeks after the stem cell
transplants showed the animals were able to use their forelimbs more
normally than rats with similarly damaged brain regions that had not
received the transplants.
"The great thing about these cells is that they are available in
unlimited supply and are very versatile," Daadi said. The neural
cells the group generated grew indefinitely in the lab and could be
an ongoing source of cells for treating stroke or other injuries, he
added.
In previous studies, Steinberg and others have implanted cells from
cord blood, bone marrow, fetal and adult brain tissue or cells
derived from mouse embryonic stem cells into stroke-damaged rats, but
none of those cell types appear as promising as the cells in this
study, the researchers said. Those cells aren't as easy to produce in
large scale, don't repair damage as effectively and are prone to
forming tumors.
Before researchers can begin testing these neural cells in human
stroke patients, Steinberg and Daadi said they need to verify that
the cells are effective in other animal stroke models and don't form
tumors. They are working with industry groups to grow the cells in
accordance with U.S. Food and Drug Administration guidelines, which
would be necessary before they could move on to human trials.
The human embryonic stem cells from which the neural cells were
derived came from stem cell lines approved for federal funding.
The work was funded by the National Institutes of Health; Russell and
Elizabeth Siegelman; Bernard and Ronni Lacroute; the William Randolph
Hearst Foundation; the Edward E. Hills Fund; and Gerald and Marjorie
Burnett.
Journal reference: Daadi MM, Maag A-L, Steinberg GK (2008) Adherent
Self-Renewable Human Embryonic Stem Cell-Derived Neural Stem Cell
Line: Functional Engraftment in Experimental Stroke Model. PLoS One 3
(2): e1644. doi:10.1371/
Adapted from materials provided by Stanford University School of
Medicine.
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MLA Stanford University School of Medicine (2008, February 19).
Human Stem Cells Aid Stroke Recovery In Rats. ScienceDaily. Retrieved
February 20, 2008, from http://www.scienced
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StemCells subscribers may also be interested in these sites:
Children's Neurobiological Solutions
http://www.CNSfoundation.org/
Cord Blood Registry
http://www.CordBlood.com/at.cgi?a=150123
The CNS Healing Group
http://groups.yahoo.com/group/CNS_Healing
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