Process
paves way for research, possible treatments of multiple sclerosis and more
Sunday, 25 September 2011
Scientists at Case Western Reserve University School of
Medicine found a way to rapidly produce pure populations of cells that grow
into the protective myelin coating on nerves in mice. Their process opens a
door to research and potential treatments for multiple sclerosis, cerebral
palsy and other demyelinating diseases afflicting millions of people worldwide.
The findings will be published in the
online issue of Nature Methods, Sunday, Sept. 25.
"The
mouse cells that we utilized, which are pluripotent epiblast stem cells, can
make any cell type in body," Paul Tesar, an
assistant professor of genetics at Case Western Reserve and senior author of
the study, explained.
"So
our goal was to devise precise methods to specifically turn them into pure
populations of myelinating cells, called oligodendrocyte progenitor cells, or
OPCs."
Their success holds promise for basic
research and beyond.
"The
ability of these methods to produce functional cells that restore myelin in
diseased mice provides a solid framework for the ability to produce analogous
human cells for use in the clinic," said
Robert H. Miller, vice dean for research at the school of medicine and an
author of the paper.
Tesar worked with CWRU School of
Medicine researchers Fadi J. Najm, Shreya Nayak, and Peter C. Scacheri, from
the department of genetics; Anita Zaremba, Andrew V. Caprariello and Miller,
from the department of neurosciences; and with Eric. C. Freundt, now at the
University of Tampa.
Myelin protects nerve axons and
provides insulation needed for signals to pass along nerves intact. Loss of the
coating results in damage to nerves and diminished signal-carrying capacity,
which can be expressed outwardly in symptoms such as loss of coordination and
cognitive function.
Scientists believe that manipulating a
patient's own OPCs or transplanting OPCs could be a way to restore myelin.
And, they have long known that
pluripotent stem cells have the potential to differentiate into OPCs. But,
efforts to push stem cells in that direction have resulted in a mix of cell
types, unsuitable for studying the developmental process that produces myelin,
or to be used in therapies.
Tesar and colleagues are now able to
direct mouse stem cells into oligodendrocyte progenitor cells in just 10 days.
The team's success relied upon guiding the cells through specific stages that
match those that occur during normal embryonic development.
First, stem cells in a petri dish are
treated with molecules to direct them to become the most primitive cells in the
nervous system. These cells then organize into structures called neural
rosettes reminiscent of the developing brain and spinal cord.
To produce OPCs, the neural rosettes
are then treated with a defined set of signaling proteins previously known to
be important for generation of OPCs in the developing spinal cord.
After this 10 day protocol, the
researchers were able to maintain the OPCs in the lab for more than a month by
growing them on a specific protein surface called laminin and adding growth
factors associated with OPC development.
The OPCs were nearly homogenous and
could be multiplied to obtain more than a trillion cells.
The OPCs were treated with thyroid
hormone, which is key to regulating the transition of the OPCs to
oligodendrocytes. The result was the OPCs stopped proliferating and turned into
oligodendrocytes within four days.
Testing on nerves lacking myelin, both
on the lab bench and in diseased mouse models, showed the OPCs derived from the
process flourished into oligodendrocytes and restored normal myelin within
days, demonstrating their potential use in therapeutic transplants.
Because they are able to produce
considerable numbers of OPCs – a capability that up until now has been lacking –
the researchers have created a platform for discovering modulators of
oligodendrocyte differentiation and myelination. This may be useful for
developing drugs to turn a patient's own cells into myelinating cells to
counter disease.
Source:
Case Western Reserve University
Contact:
Kevin Mayhood .........
For more on stem cells and cloning, go to CellNEWS at
http://cellnews-blog.blogspot.com/
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