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 fibres, called axons, grow longer in
response to the strain.
In addition, the researchers have grown these
elongated nerve fibres directly on a dissolvable
membrane, ready-made for transplant. Their
discovery is published in the April edition of
Tissue Engineering.
According to Douglas Smith, MD, lead researcher
on the project and associate professor in the Penn
Department of Neurosurgery, 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. 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.
According to Smith, once somebody's nervous
system is already formed, further outgrowth could
cause mass confusion, so the body actively
produces chemicals that stop axon growth.
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 centimetre 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 centimetre. Smith, however, could find
no physiological reason why they could not be
stretched even further.
The scientists believe that, as pressure is put
on the axons from either end, the axon begins to
add a little to its own internal skeleton in
response.
During these experiments, Smith noticed another
curious phenomenon. He began to see that the
stretch-grown neurons could actually organize
themselves into bundles, nerve fibres composed of
thousands of axons 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 bridges
to rewire damaged nervous tissue.
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.
Smith concedes that the idea itself may seem
like a stretch, but scientists are only at the
beginning of learning what can be done with this
concept.
http://unisci.com/stories/20012/0418011.htm