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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.