| April 17, 2001
Penn Researchers
Discover That Stretching Neurons Induces Growth
Scientists Foresee Bridging Nerve Damage with
Grafts
(Philadelphia,
PA) - They say that tension is bad for the nerves, but
it turns out that a little applied tension might be
good for nerve cells. Researchers at the University
of Pennsylvania Medical Center have been able to grow
nerve cells, or neurons, by stretching them - offering
a new means of bridging damaged areas of the nervous
system.
Using a motorized device to slowly pull connected neurons
away from each other, the Penn researchers have discovered
that the connecting nerve fibers, called axons, grow
longer in response to the strain. In addition, the researchers
have grown these elongated nerve fibers directly on
a dissolvable membrane, ready-made for transplant. Their
discovery is published in the April edition of Tissue
Engineering.
"Most studies have examined axon growth in terms
of how axons sprout from one neuron and connect to another.
But there is an equally important form of axon growth
that has been overlooked, the growth of axons in terms
of the growth of the entire organism," said Douglas
Smith, MD, lead researcher on the project and associate
professor in the Penn Department of Neurosurgery. "In
a way, stretching is akin to how nerve cells grow in
developing children - as they get taller their axons
get longer."
These findings, which have evolved from Smith's ongoing
research into how neurons respond to their environment,
also represent a departure from other methods of restoring
neural pathways in spinal cord injuries by bridging
over damaged tissue. One approach has been to transplant
a synthetic scaffolding across the injured area and
then use a trail of attractive chemicals to entice axons
to grow out from one end of the lesion and connect with
viable nervous tissue on the other side. While these
attempts have had limited success in the laboratory,
they have been hampered in live subjects by, among other
things, the body's innate desire to stop neuron outgrowth.
"Once somebody's nervous system is already formed,
further outgrowth could cause mass confusion, so the
body actively produces chemicals that stop axon growth"
said Smith.
But it was the inherent ability of axons that were already
connected to grow during natural development that gave
the researchers the idea to stretch axons in culture.
Smith and his colleagues began with a group of neurons
grown in a culture across two membranes. Using a motor
that could function in precise increments, they separated
the two membranes by a few thousandths of a centimeter
every few minutes. A small distance on a human level,
but a remarkably large distance on the cellular level.
Eventually, as they describe in Tissue Engineering,
they were able to stretch the neurons an entire centimeter.
Smith, however, could find no physiological reason why
they could not be stretched even further.
"We believe that, as we put pressure on the axons
from either end, the axon begins to add a little to
its own internal skeleton in response," said Smith.
"It is sort of like the little boy who tries to
get taller by having his siblings pull on his limbs,
only in this case it seems to work."
During these experiments, Smith noticed another curious
phenomena. "We began to see that the stretch-grown
neurons could actually organize themselves into bundles,
nerve fibers of composed of thousands of axons,"
said Smith, "and these bundles gradually consolidated
into even larger tracts."
Accordingly, these large tracts could serve as the bridge
across damaged tissue, connecting either side and allowing
the nerve signal to cross. In fact, researchers would
likely not have to modify the stretched neurons before
transplanting - the body easily absorbs the membranes
used in the stretching process. As with all strategies
to bridge nerve damage, Smith hopes that the neuron's
own innate ability to connect will allow transplantable
axon bridge to rewire damaged nervous tissue.
"Axons are promiscuous little things," said
Smith, "and we're counting on their innate tendency
to feel around and make new connections."
In addition to spinal cord repair, Smith conceives of
using the elongated axon cultures as a bridge for other
types of neural injuries affecting long axon tracts,
including optic nerve damage and peripheral nerve damage.
"The idea itself may seem like a stretch,"
said Smith, "but we are only at the beginning of
learning what we can do with this concept."
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