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Aleksandra Sabov
End of the Year Essay
Dean Grosvsky
Gateway Seminar
Stem Cells in the Nervous System
It is currently known that nerve cells do not regenerate. Based on this and new research in
stem cells regarding the nervous system; there are several different research studies being
done or that have been already conducted in regarding the nervous system and stem cells,
which show promise in being able to regenerate neurons and restore function.
As an introduction, the nervous system consists of the spinal chord, brain,
and nerves. These organs are composed of neurons, which send signals throughout the
body, and also glial cells, which aid in the speeding of signals over long distances. If
these glial cells are damaged, signals take longer to reach their destinations in the body
and this can cause detrimental effects. Many who have been involved in a car accident or
other traumas involving head or spinal injuries have impaired function in their muscles as
well as a decrease in sensation. (Nih)
Currently, a lot of research is going into learning about whether or not
stem cells can replace cells in the brain, treating neurological diseases. The idea is that
the malfunctioning cells in the brain would be removed, and replaced with functioning
stem cells in order to replace the system and bring the brain to full function once again.
The idea is simple, but many things go into the experimentation and
research behind whether or not these stem cells will function as replacements. The stem
cells used as replacements must be able to create authentic replacement neurons in order
to provide proper function. Once it is determined that these replacement neurons are
sufficient, it must be determined whether or not the cells can be recreated in a laboratory.
The neurons then must be tested in animals to make sure they function correctly and do
not produce cell overgrowth or disease.
Unfortunately, in previous trials authentic neurons have not been created.
The neurons produced only look like the ones needed, but are missing major
characteristics, providing no help to the patient. In order for the neurons to actually help
the patient, they must “be electrically excitable, release the appropriate neurotransmitter,
have the right genetic markers switched on, make neural structures like processes and
synapses and have a functional effect in models of disease” (Barker).
There have been several different attempts in treating spinal injuries with
stem cells. One of the largest clinical trials for treating spinal injuries was involving the
company Geron. They were the first company to be cleared by the FDA to use
GRNOPC1. GRNOPC1 was derived from human embryonic stem cells derived
oligodendrocyte progenitor cells, which were injected into the direct site of the injury.
This prompted a new way of looking at how to heal acute spinal injuries. Instead of
prescribing a drug, this type of treatment would introduce replacement cells to restore
tissues, which would then restore function. Unfortunately the company shut down in the
middle of this study. They are still collecting data from the participants that were are
already in the program,but are not introducing any more new subjects into the study.
On the other hand, the FDA approved another stem cell driven company,
Asteria, to perform a thirteen person study in which the same oligodendrocyte progenitor
cells would be used. There are several differences between the two studies. Asteria will
give their participants a ten time stronger dosage. Also, they will look at patients that
have had injuries originating closer to the neck rather than the spine. This trial will start
recruiting people in early 2015.
There has been a study conducted at the University of Pittsburgh School of
Medicine propagates that muscle-derived stem cells taken from the site of neuron
damage, when grown in a medium suitable for nerve cells, could differentiate into
neurons and glial cells. These glial cells also include Schwann cells, which form the
myelin sheath. This myelin sheath is the main structure that aids in the speeding up of
signal transport. An experiment was done on mice, in which their sciatic nerves was
damaged and human muscle derived stem cells were placed at this site. After 12 weeks,
the nerve had completely regenerated in the treated mice, but not in the untreated mice.
This shows that stem cells derived from muscle cells can help regenerate nerve cells.
Now researchers are trying to discover what in the human muscle cells triggered injury
repair.
Stems cells can be helpful in neurological disorders as well. They can help
in other ways than just making neurons. Instead of replacing damaged cells, stem cells
can provide more of a support system to the already diseased cells. This will help them to
survive and not progress further and possibly recover. This is an important process that
has been theorized and studies that have been conducted, which show that stem cells can
aid in recovery od these degenerated areas.
Parkinson’s is a disease which results in cell death in the nervous region
called the substantia nigra. This disease affects about two percent of all adults over sixtyfive years old. The cells of the substantia nigra release dopamine, which is a neuro-
transmitter, which aids in motor function. Since these cells are dying, the production of
dopamine in reduced and thus motor function significantly decreased. There is a nonstem cell treatment, which involves the use of a drug by the name of levodopa, also
known as L-dopa. The administration of this drug results in the brain converting and
breaking down the substance and releasing it as dopamine. The drug works well initially,
but then starts to have a reverse effect causing the side effects to worsen and the
Parkinson’s to become even more progressed. (Panchision)
There are also ways in which stem cells are being used to potentially treat
Parkinson’s. One way is by taking fetal tissue from mice and transplanting the tissue into
an adult rat eye, which has had Parkinson’s induced in it. The results from these trials
showed that the tissues would develop into mature neurons, which would function in the
way they were suppose to. The newly developed neurons were found to produce
dopamine and reduce or reverse symptoms of Parkinson’s in rats and monkeys when
placed into the damaged areas.(Nih)
There have also been 2 large scale trials in humans, which have happened
in the past 15 years. One of them was conducted in New York and the other one in
Colorado. In these trials, researchers transplanted tissue from aborted fetuses into the
striatum of patients with Parkinson's disease. Many patients didn’t see results, but the
ones who did were younger patients who had milder symptoms in the beginning, which
made them respond well to the grafts. Scans of the brain showed that the neurons had
matured and the production of dopamine had increased.
Another study, which involved the grafting of cells both into the striatum
(the target of dopamine neurons) and the substantia nigra (where dopamine neurons
normally reside) of three patients showed no adverse effects and some modest
improvement in patient movement. (Panchision)
We have come to the conclusion that based on the research that is being
done to find a way in which nerve damage can be restored; there are high hopes for
patients with these degenerative neurological disorders. Through the use of stem cells,
patients may be able to replace damaged nerves and even regenerate the ones that have
already been damaged without actually replacing them. We are a long way from finding
solutions to all the kinks in the current findings,but with the little bit of progress that has
been made in studies shown, such as with Parkinson’s and spinal chord injuries , we can
see that there might me a future in using stem cell as a form of treatment down the road.