Regenerating Tissues Essay, Research Paper
The ability to regenerate the tissues of the human central nervous system
(CNS) is one of the greatest projects undertaken by biomedical engineers
today. With this eventual technology, permanent paralysis and blindness
due to CNS injury will be a thing of the past. Central nervous system
injuries will be repairable, an idea that was, until recently, just a
fanciful dream, something out of a science fiction novel.
In the last few years, however, giant strides have been made to make the
idea of CNS regeneration a reality within the grasp of engineers and
doctors alike. This technology has advanced to the point where successful
tests are being performed on lower level adult mammals. If all continues
to go well, human implementation may soon follow.
The axons of the central nervous system in adult mammals do not regenerate
spontaneously after injury, mainly because of the presence of
oligodendrocytes that inhibit axonal growth. These glial cells block the
growth of the axons in the central nervous system, preventing any kind of
regeneration within the CNS.
What was discovered, through experimentation, was that lower non-mammalian
vertebrates could regenerate their central nervous system after injury.
Regeneration of the optic nerve occurs spontaneously in fish. This
phenomenon has been correlated to the presence of factors that are toxic
to oligodendrocytes. This substance is closely related to interleukin-2.
Lower level mammals, on the other hand, are, like humans, unable to
regenerate their CNS. The same experiment performed on the fish above
yielded completely different results when done on adult mammals. Severing
of the optic nerve near the eye is followed by a loss of retinal ganglion
cells combined with a failure of axons to regrow into the brain.
Further experimentation found that by manipulating the environment around
the injured retinal ganglion cells, increases the survival rate of
neurons, and make lengthy axonal regeneration, that restores nerve
function to the injured area, possible. This discovery suggested that
that injured nerve cells in the mature mammal CNS are influenced by
interactions with their immediate environment. In certain conditions,
injured central nervous system neurons can resemble normally developing
neurons, and return to a functioning state.
The restoration of connections in the injured CNS of adult mammals is
aided by a guided channeling of the injured axons along a transplanted
segment of peripheral nerve. These neurons recover their capacity to form
synapses along their former channel. These peripheral nerve grafts
increase the survival rate of severed neurons in adult rats twenty
percent. Some of these neurons returned to a fully functional form,
making complete synaptic connections with other neurons.
To explore further the capacity of damaged CNS neurons to initiate and
sustain fiber growth, PN grafts were first applied to the spine of adult
rats. After six to forty two weeks, the range in which the CNS and PN
grafts have been known to integrate, the rats’ spines were crushed.
Investigated four to eleven weeks later, it was shown that these grafts
had significantly helped the regeneration of the spinal cord. The number
and distribution of neurons in the crushed areas of the rats’ spines was
found to be similar to that of the uncrushed regions. This suggests that
central neurons whose axons are grafted with peripheral nerve cells are
capable of renewed growth after injury. Under these experimental
conditions, CNS neurons respond to injury in a similar manner to
peripheral nerve cells.
Another hypothesis was made, that suggested that axons could only
regenerate when their growing tips are surrounded by extracellular fluid
containing proteins from the blood. An experiment was done on fetal rat
explants to test the hypothesis. The explants were cultured in serum
medium for ten days, followed by an eight day period in a serum free
medium. It was found that all explants cultured in serum medium for ten
days showed a greater than seventy seven percent viability. The explants
that were kept in the serum for eight more days retained their viability
rate, while the viability rate for the explants that were placed in the
serum free environment dropped to seven and a half percent. Electron
microscope analysis, showed that tissue viability was above seventy five
percent in all explants, indicating that serum is important only to axon
growth and not neuron survival . This data strengthened the hypothesis
that blood derived proteins were needed for prolonged regen!
eration.
There are certain cells, found in the peripheral nervous system, that
undertake a broad field of tasks in the peripheral nervous system. Called
Schwann cells, they regulate ensheathment and myelination, they are
involved in extracellular matrix production, and they are also
instrumental in the promotion of peripheral nervous system regeneration by
remyelating axons and restoring electrophysiological conduction. Along
with astrocytes, which provide nutritional proteins for the regeneration
of axons, these two cells are primarily responsible for peripheral nervous
system regeneration.
The conjecture that was made next was that these Schwann cells were the
reason that the peripheral graft experiments went so well. The Schwann
cells and astrocytes were helping to rebuild not only the peripheral
nerves that had been crushed, but the CNS neurons as well.
Another experiment was done on rats to determine whether or not the
Schwann cells were responsible for the regeneration in the peripheral
nervous system. Semipermeable nerve guidance channels were prepared,
inserted to connect to ends of a severed peripheral nerve, and the seeded
with astrocytes, Schwann cells, or a mixture of the two. The astrocytes
alone, impeded regeneration, while the Schwann cells increased the amount
of growth. The combination of the two worked as well, provided that the
Schwann cells out numbered the astrocytes.
Taking this into account, the latest move has been to attempt to create
nerve guidance channels for the central nervous system. Using the all the
previous research in the field, biomedical engineers have designed and
created a device that is being tested in animals right now. Using a nerve
guidance channel filled with agarose hydrogel, a gel-like medium ideal for
nerve regeneration and excellent at conducting electricity, this channel
is inserted into the body at the site of CNS injury. Each separated end
of the nerve is enclosed in the guidance channel, and then the channel is
seeded with Schwann cells, astrocytes, proteins to nourish the growing
nerve, and interleukin-2, to destroy the inhibiting Oligodendrocytes.
If this works, we may soon be able to cure paralysis and some types of
blindness. Mankind will make another great stride forward in the field of
medicine, curing another seemingly incurable affliction. This technology
will be an achievement of utmost magnitude and importance, and we will all
benefit from the realization of something that, until recently was just a
pipe dream.
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