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Scientists
at Northwestern University have designed synthetic molecules that promote
neuron growth, a promising development that could lead to the reversal of paralysis
due to spinal cord injury.
“We have created new materials that because of
their chemical structure interact with cells of the central nervous system in
ways that may help prevent the formation of the scar that is often linked to
paralysis after spinal cord injury,” said Samuel I. Stupp, Board of Trustees
Professor of Materials Science and Engineering, Chemistry and Medicine.
Similar to earlier experiments that promoted bone growth,
the scientists now have successfully grown nerve cells using an artificial three-dimensional
network of nanofibers, an important technique in regenerative medicine. The
results were published online by the journal Science.
The
gel formed when 1% of an aqueous IKVAV-PA solution is mixed with cell media
on a glass cover slip (12mm). Under these physiological conditions the IKVAV-PA
self-assembles into nanofibers which interact to cause macroscopic gel formation.
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“We have
shown that our scaffold selectively and rapidly directs cell differentiation,
driving neural progenitor cells to become neurons and not astrocytes,”
said Stupp, who led the research team in Evanston. “Astrocytes are
a major problem in spinal cord injury because they lead to scarring and
act as a barrier to neuron repair.”
The innovative scaffold is made up of nanofibers formed
by peptide amphiphile molecules. The scientists’ key breakthrough
was designing the peptide amphiphiles so that when they self-assembled
into the scaffold a specific sequence of five amino acids known to promote
neuron growth were presented in enormous density on the outer surfaces.
“This was all done by design,” said
Stupp, who is also director of the University’s Institute for Bioengineering
and Nanoscience in Advanced Medicine. “By including a specific biological
signal on the nanostructure we were able to customize the new materials
for neurons.”
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In collaboration with the lab of John A. Kessler, Benjamin and Virginia T.
Boshes Professor of Neurology at the Feinberg School of Medicine, Stupp and
his team observed that when the peptide amphiphiles were placed in solution
and combined with neural progenitor cells (which are present in the central
nervous system and able to differentiate into different types of cells) the
nanofiber scaffolds formed and led quickly to the selective differentiation
of the cells into neurons.
In subsequent experiments, the researchers successfully delivered the peptide
amphiphile solution, using a simple injection, to the site of a spinal cord
injury in a laboratory rat. Upon contact with the tissue, the solution was transformed
into a solid scaffold.
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In addition to Stupp and Kessler, other authors
on the Science paper are Gabriel A. Silva and Catherine Czeisler (lead
authors), Krista L. Niece, Elia Beniash and Daniel Harrington, all from
Northwestern University. The research was supported by the National Science
Foundation, the National Institutes of Health and the U.S. Department
of Energy.
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| A scanning electron micrograph
of the nanofiber gel with the water removed. |
Posted 3rd February 2004
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