Human stem cells show promise against fatal children's diseases
Scientists have used human stem cells to dramatically improve the
condition of mice with a neurological condition similar to a set of
diseases in children that are invariably fatal, according to an
article in the June issue of the journal Cell Stem Cell.
With a one-time injection of stem cells just after birth, scientists
were able to repair defective wiring throughout the brain and spinal
cord – the entire central nervous system – of mutant "shiverer mice,"
so called because of the way they shake and wobble. The work marks an
important step toward the day when stem cells become an option for
the treatment of neurological diseases in people.
Neuroscientists at the University of Rochester Medical Center
injected a type of fetal human stem cell known as glial stem cells
into newborn mice born with a condition that normally claims their
lives within about 20 weeks of birth, after a lifetime of seizures
and other serious consequences. While most of the 26 mice that
received transplanted glial stem cells still died, a group of six
lived far beyond their usual lifespan, and four appeared to be
completely cured – a first for shiverer mice. The scientists plan to
gather more evidence before trying the approach in sick children.
"It's extremely exciting to think about not only treating but
actually curing a disease, particularly an awful disease that affects
children," said neurologist Steven Goldman, M.D., Ph.D., a leader in
manipulating stem cells to treat diseases of the nervous
system. "Unfortunately, right now, we can do little more for many of
these conditions besides tell parents to prepare for their kids to
die."
Thousands of children with rare, fatal disorders known as pediatric
leukodystrophies share a central problem with the shiverer mice:
Their brain cells lack sufficient myelin, a vital fatty coating that
wraps around cells in the brain like insulation around an electrical
wire. Myelin coats long sections, known as axons, of brain cells
called neurons, and without it, the electrical signaling between
neurons becomes sluggish and muddied, causing a variety of symptoms.
Myelin loss is at the heart of multiple sclerosis, and also plays a
role in the symptoms of diabetes, high blood pressure, and other
diseases.
In children, diseases of myelin go by a host of names but share the
same features: a childhood and young adulthood that may include
weakness, difficulty standing or walking, seizures, dementia,
paralysis, and ultimately, death. These diseases, which include Tay-
Sachs, Krabbe's, Canavan's, Pelizaeus-Merzbache
Matter Disease and a host of others are each rare, but collectively
they kill thousands of children every year. Just last week, Lorenzo
Odone, whose battle with one such disease, adrenoleukodystroph
featured in the film Lorenzo's Oil, passed away. Currently there is
no treatment for any of these conditions.
Goldman and first author and scientist Martha Windrem have been
working on shiverer mice for more than a decade. In work published in
2004 in Nature Medicine, the team restored myelin in a widespread
area of an animal's brain, by injecting human stem cells that
eventually become oligodendrocytes, the cells that produce myelin. In
those earlier experiments, the team attempted to repair cells in only
certain parts of the brain. Although the methods were effective, the
treatment didn't actually improve the health of the mice.
In the latest work, the team took advantage of the routes that cells
commonly take to migrate from one region of the brain to another.
They injected approximately 300,000 human stem cells into the brain
of each mouse, choosing five particular spots because of their
ability to serve as launch pads of sorts for stem cells to migrate
and colonize the entire brain and spinal cord.
And that's just what happened in some of the mice. In just two
months, the glial stem cells multiplied and spread, covering nerve
cells in almost the entire central nervous system, exactly mirroring
their distribution in the brains of healthy mice. For several months
after that, the cells produced myelin that coated nerve cells
throughout the entire brain and spinal cord; from then on, the brain
cells functioned normally, conducting impulses as quickly as in
normal mice.
Not all of the transplanted mice fared well. Of 26 mice treated with
stem cells, about three-quarters died, typically from seizures,
within a couple of weeks of their untreated counterparts. But the six
treated mice that lived longer recuperated to a degree hardly thought
possible. The four mice that still survived one year after treatment
improved rapidly, had no seizures, and were practically free of
symptoms.
"We kept expecting them to die. Not only did they not die, but they
improved day by day," said Goldman, who is director of the Center for
Translational Neuromedicine and professor of Neurosurgery and
Neurology.
The stem cells established themselves and spread throughout the brain
with similar success in all the transplanted mice, including the ones
that died near the time of their untreated counterparts. So why did
some mice live longer? Goldman believes it was a race against time:
Many of the mice were so sick that constant seizures killed them
before the stem cells could take hold, propagate, spread, and
remyelinate brain cells.
###
The work was made possible thanks to funding from the Adelson Medical
Research Foundation, the Mathers Charitable Foundation, the National
Multiple Sclerosis Society, the CNS Foundation, the Ataxia-
Telangiectasia Children's Project, and the National Institute of
Neurological Disorders and Stroke
In addition to Windrem and Goldman, other Rochester authors of the
paper include Steve Schanz; Min Guo, Ph.D.; Vaughn Washco; Su Wang,
Ph.D.; Guo-Feng Tian, Ph.D.; Maiken Nedergaard, M.D., Ph.D.; and
Nancy Stanwood, M.D. Other authors include Matthew Rasband of the
Baylor College of Medicine, Neeta Roy of Weill Cornell Medical
Center, and Leif Havton of UCLA.
Public release date: 4-Jun-2008
Contact: Tom Rickey
tom_rickey@urmc.
585-275-7954
University of Rochester Medical Center
http://www.eurekale
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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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