Main Category: Stem Cell Research
Included In: Multiple Sclerosis
Article Date: 05 Jun
2008 - 12:00 PDT
Scientists in the US have used human cells that behave like stem cells to help
"shiverer" mice grow myelin around their nerve fibres and thereby avoid an
inevitable early death and poor quality of life; the researchers hope their
finding will one day lead to treatments for similar neurological conditions in
humans, and children especially.
The research is the work of
neuroscientists at the University of Rochester Medical Center, New York, and is
published in the June issue of the journal Cell Stem Cell.
fattly myelin sheath that surrounds long fibre-like sections (axons) of nerve
cells in the brain and spinal cord is like insulation around electrical wires -
it stops leakage of electrical impulses that control vital body functions
including movement. Insufficient or poorly working myelin causes a number of
diseases, including a rare and fatal congenital disorder called pediatric
leukodystrophy that affects thousands of children.
Like "shiverer" mice,
so-called because they shake and wobble, children with pediatric leukodystrophy
don't have enough myelin around their axons, and so the electrical impulses
become weak and distorted, causing symptoms like difficulty standing and
walking, seizures, dementia, paralysis, and eventually death. These are also the
symptoms of other similar fatal, rare and equally uncurable childhood diseases
such as Tay-Sachs, Krabbe's, Canavan's, Pelizaeus-Merzbacher, Vanishing White
Matter Disease, and others.
Last week Lorenzo Odone, whose plight and
courage, as well as the determination of his parents, was portrayed in the film
Lorenzo's Oil, died from another such disease,
Myelin loss is also the reason for multiple
sclerosis, and occurs to some extent in other diseases like diabetes and high
Study author and neurologist Dr Steven Goldman, is a
leader in using stem cells to treat diseases of the nervous system. For this
study, he and first author and scientist Dr Martha Windrem, who have been
working on shiverer mice for over ten years, together with other colleagues,
used a type of fetal human cell known as glial stem cells or glial progenitor
cells. They are not quite like embryonic stem cells because they don't have the
potential to become any type of cell in the body, they can only produce a
limited range, including oligodendrocytes, the cells that make
The researchers injected the glial stem cells into 26 newborn
shiverer mice that had been genetically programmed to have the condition, which
normally results in early death about 20 weeks later, and a low quality of life
characterized by seizures and other serious symptoms.
Most of the mice
still died at the age typical for the disease, but six of them lived much
longer, of which four appeared to be completely cured, something that has never
been achieved before with shiverer mice.
Because of their experience with
shiverer mice, Goldman, Windrem and colleagues knew how many human glial cells
(around 300,000) to use in each mouse, and where to inject them in the mouse's
brain (they chose five places) to ensure they migrated to all parts of the brain
and spinal cord.
It took two months for the glial cells to multiply and
spread, throughout the whole of the central nervous system, in the same way as
they would in healthy mice. After that, they started to produce myelin, and
continued for several months, coating all the axons in the entire brain and
nervous system, until the cells were sending impulses correctly and just as
quickly as in normal mice.
Four of the six mice survived one year after
treatment, improved rapidly, had no seizures and were almost free of symptoms.
Goldman, who is Director of the Center for Translational Neuromedicine
and professor of Neurosurgery and Neurology at Rochester, said:
expecting them to die. Not only did they not die, but they improved day by
Speculating as to why some mice lived longer and others died,
Goldman said it was probably a race against time. For many of the mice, constant
seizures killed them before the glial cells could settle and proliferate, they
were too sick.
Goldman said he was very excited about the prospect of
their findings leading not only to treatment but perhaps even a cure for the
awful diseases that affect children.
But it will be some time before any
treatments are developed and trialled, never mind be ready in time to help the
thousands that are suffering today:
"Unfortunately, right now, we can do
little more for many of these conditions besides tell parents to prepare for
their kids to die," said Goldman.
"Neonatal Chimerization with
Human Glial Progenitor Cells Can Both Remyelinate and Rescue the Otherwise
Lethally Hypomyelinated Shiverer Mouse."
Martha S. Windrem, Steven J.
Schanz, Min Guo, Guo-Feng Tian, Vaughn Washco, Nancy Stanwood, Matthew Rasband,
Neeta S. Roy, Maiken Nedergaard, Leif A. Havton, Su Wang, and Steven A.
Cell Stem Cell, Vol 2, 553-565, 05 June 2008.