"This is the first time this has been done with non-embryonic stem
cells," says James Hickman, a University of Central Florida bioengineer
and leader of the research group, whose accomplishment is described in
the Jan. 18 issue of the journal ACS Chemical Neuroscience.
James Hickman.
"We're very excited about where this could lead because it overcomes many of the obstacles present with embryonic stem cells."
Stem cells from umbilical cords do not pose an ethical dilemma
because the cells come from a source that would otherwise be discarded.
Another major benefit is that umbilical cells generally have not been
found to cause immune reactions, which would simplify their potential
use in medical treatments.
The pharmaceutical company Geron, based in Menlo Park, Calif.,
developed a treatment for spinal cord repair based on embryonic stem
cells, but it took the company 18 months to get approval from the FDA
for human trials due in large part to the ethical and public concerns
tied to human embryonic stem cell research. This and other problems
recently led to the company shutting down its embryonic stem cell
division, highlighting the need for other alternatives.
Sensitive Cells
The main challenge in working with stem cells is figuring out the
chemical or other triggers that will convince them to convert into a
desired cell type. When the new paper's lead author, Hedvika Davis, a
postdoctoral researcher in Hickman's lab, set out to transform umbilical
stem cells into oligodendrocytes -- critical structural cells that
insulate nerves in the brain and spinal cord -- she looked for clues
from past research.
Davis learned that other research groups had found components on
oligodendrocytes that bind with the hormone norephinephrine, suggesting
the cells normally interact with this chemical and that it might be one
of the factors that stimulates their production. So, she decided this
would be a good starting point.
In early tests, she found that norepinephrine, along with other stem
cell growth promoters, caused the umbilical stem cells to convert, or
differentiate, into oligodendrocytes. However, that conversion only went
so far. The cells grew but then stopped short of reaching a level
similar to what's found in the human nervous system.
Davis decided that, in addition to chemistry, the physical environment might be critical.
To more closely approximate the physical restrictions cells face in
the body, Davis set up a more confined, three-dimensional environment,
growing cells on top of a microscope slide, but with a glass slide above
them. Only after making this change, and while still providing the
norephinphrine and other chemicals, would the cells fully mature into
oligodendrocytes.
"We realized that the stem cells are very sensitive to environmental conditions," Davis said.
Medical Potential
This growth of oligodendrocytes, while crucial, is only a first step
to potential medical treatments. There are two main options the group
hopes to pursue through further research. The first is that the cells
could be injected into the body at the point of a spinal cord injury to
promote repair.
Another intriguing possibility for the Hickman team's work relates to
multiple sclerosis and similar conditions. "Multiple sclerosis is one
of the holy grails for this kind of research," said Hickman, whose group
is collaborating with Stephen Lambert at UCF's medical school, another
of the paper's authors.
Oligodendrocytes produce myelin, which insulates nerve cells, making
it possible for them to conduct the electrical signals that guide
movement and other functions. Loss of myelin leads to multiple sclerosis
and other related conditions such as diabetic neuropathy.
The injection of new, healthy oligodendrocytes might improve the
condition of patients suffering from such diseases. The teams are also
hoping to develop the techniques needed to grow oligodendrocytes in the
lab to use as a model system both for better understanding the loss and
restoration of myelin and for testing potential new treatments.
"We want to do both," Hickman said. "We want to use a model system to
understand what's going on and also to look for possible therapies to
repair some of the damage, and we think there is great potential in both
directions."
Besides Hickman and Davis, the other authors on the paper were
Xiufang Guo, Stephen Lambert, and Maria Stancescu, all from the
University of Central Florida.
From sciencedaily
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