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Adult Stem Cell Research and its effect on the Treatment of Multiple Sclerosis
Chapter 1: Introduction
About 2.5 million people worldwide have been diagnosed with multiple sclerosis (MS), and because it is a neurological autoimmune disease, many people living with MS are left with long term nerve damage and or permanent disability (The Myelin Project). Yet, surprisingly very little is known about this debilitating disease. Currently there is no known cause, no effective means of prevention, and no cure for it, which is amazing considering it is the most common chronic neurological disorder in developed countries. Recently the scientific community has started exploring the possibility of regenerating nerves that have been significantly damaged or destroyed by MS through various biotechnological approaches. One of the most promising biotechnological approaches for nerve regeneration being explored is adult stem cell therapy. If adult stem cell therapy is successful in remyelinating and or regenerating nerves it could repair central nervous system damage caused by MS and could greatly increase our understanding of what triggers MS and what mechanisms MS uses to attack the nerve cells of the human body.
In order to understand how nerve regeneration can aid in the treatment of multiple sclerosis it is necessary to understand what MS is and how it affects the body. To further examine what MS does to the body, it is also important to have at least a basic understanding of how nerves and the immune system function under normal conditions as well as a general understanding of how the central nervous system (CNS) works and some basic principles behind the genetic issues associated with the development of MS.
Chapter 2: “What is multiple sclerosis?”
Due to the complex nature of MS, it is helpful to have a working definition of the disease before attempting to explain how it functions. Multiple sclerosis is a chronic demyelinating disorder in which white blood cells of the immune system (T-cells) invade the CNS and destroy the myelin of neurons causing plaque, or scar tissue, to build up around the damaged neurons (see diagrams 1 and 2). In fact, multiple sclerosis is named after this process: “multiple” meaning many and “sclerosis” referring to the scarring of neurons. Because myelin functions as an insulator for neural transmissions, it is very difficult for neurons that have been damaged to properly conduct and transmit signals. Thus people with MS tend to experience many neurological abnormalities such as paralysis, vision loss, difficulty with speech, and varied tremors. Some people also experience emotional problems such as depression. This makes symptomatic treatment of MS patients very hard in that symptoms exhibited tend to vary widely among individuals and can even vary within a particular individual from time to time. There are four different courses MS can take: Relapsing-Remitting, Primary-Progressive, Secondary-Progressive, and Progressive-Relapsing. Each of these sub-classes is identified by differing characteristics such as exacerbation rate, with Relapsing-Remitting having the more temporary exacerbations and Progressive-Relapsing being classified with having long periods of steady decline (National MS Society). In short, the symptoms of this disease can be as unique as the individuals who suffer from it themselves.
Diagram 1 Diagram 2

Neuron under normal conditions (National MS Society) Neuron damaged by MS (National MS Society)
Chapter 3: “How does MS function?”
Although there is still no known cause of MS, research has led to a better understanding of how the disease functions. Currently it is believed that T-cells play a key role in the degeneration of myelin and axonal damage that occurs during MS exacerbations. Exacerbations are periods of acute decline of neurological function which are usually temporary. Typically, T-cells participate in normal immune system functions such as ridding the body of infected cells or pathogens, maintaining homeostasis in the immune system, and regulating white blood cell activity (Campbell). In an individual with MS for an unknown reason, these cells cannot properly differentiate between self and non-self tissue and thus turn against certain cells or molecules within the body. Normally T cells would not be able to access the CNS due to the blood-brain barrier (BBB) which is a physical barrier made up of endothelial cells that line capillaries in the brain. Endothelial cells create tight junctions between the blood and the brain and help to expedite blood flow through capillaries (Campbell). The BBB effectively prevents most substances from entering the brain and thereby prevents any drastic changes in the brain’s environment. However during MS exacerbations it has been shown through MRI scans that the BBB is somehow broken down in sections of an individual’s brain or spinal cord which allows T cells as well as other cells and soluble factors such as proteins that either stimulate or suppress white blood cells (lymphocytes) and immune system response (cytokines) and antibodies to cross over into the CNS. This creates an inflammatory response in areas of white matter in the brain and spinal cord that is very similar to what happens when the skin is broken as in a cut.
During the inflammatory response myelin gets stripped from the axons (demyelination) causing zones of damage known as lesions in the brain and spinal cord. Because myelin is made of mainly protein, inflammation causes it to denature and the result is somewhat like removing rubber insulation from a wire. Without the myelin’s insulation, nerve impulse transmissions are slowed or stopped and a neuron’s total “conductivity”, so to speak, will be greatly reduced. In order for neurons to transmit impulses in the form of action potentials to other neurons they must depolarize and repolarize their surfaces by allowing or actively transporting ions of different charges to enter and leave their membranes. If the neurons do not have an insulating layer of myelin around their axons, then action potentials cannot be carried as quickly or as efficiently as they normally would be. When signals are not transmitted properly between neurons many different types of neurological problems specific to the damaged neurons can occur. Additionally, inflammation of brain and spinal cord tissue can damage nerve axons and their ability to transmit action potentials and research seems to indicate that inflammation also has the ability to kill myelin producing oligodendrocytes and maintenance (glial) cells which help to naturally repair damage.
Generally scientists agree on this theory about how MS functions; however there are many questions about MS that remain unanswered such as: “How is the BBB broken down?”, “What triggers T-cells to attack neurons?”, and “What happens first: oligodendrocyte death or inflammation?” Many of these gaps in our understanding of how MS function have to do with the utter complexity of the CNS and the immune system and will only be truly solved once we have managed to fully map these systems. This process will likely take many years. Additionally, there is an intense debate occurring in the scientific community over what exactly occurs during remission following an exacerbation. Researchers seek to determine how best to aid natural recovery as well as what genetic or environmental factors cause MS.
Chapter 4: “What role does genetics play in MS?”
Although multiple sclerosis cannot be directly inherited from parent to offspring, there are definite correlations between the genetic predispositions of different families and populations for who does and does not develop the disease. For example, although the familial risk of developing MS is relatively low, there are instances where MS occurs
too frequently in certain families to be coincidental. Additionally, there are certain populations such as those of continental North America, Northern Europe, or Austrailasia where approximately one of every thousand people have some form of MS. In other populations like those of countries closer to the equator MS is more rare, and it may be that these populations have a genetic predisposition of resistance to the disease (National MS Society). If strong positive correlations can be drawn and scientifically proven, then it may be possible to pinpoint who is more likely to develop the disease.
Research has also proven that an individual’s immune system function is influenced by their genetics. The genes controlling an individual’s immune function may be different in people with MS and may determine which course the disease will take, i.e., the severity of the type of MS the individual develops. For instance, genes determine the assortment of major histocompatibility complexes (MHC) which are cell surface antigens that have the ability to trigger T-cell responses that can lead to the rejection of foreign tissues. Some of these complexes are associated with the development of autoimmune diseases like MS. Gene variants and their location on chromosomes can be linked to MS susceptibility. One of the genes involved in immune system activity known as the interferon gamma gene, for example, is more prevalent in women than men and this could explain why women are more susceptible to MS (mscare.com). It is also highly likely that there are several genes that play a role in the development of MS that can be inherited but must be arranged in the right order in an individual’s DNA in order for them to actually develop the disease.
Although genetics do play a role in MS, evidence suggests that there are probably more factors involved in its development such as geography, virology, bacteriology, and immunology (National MS Society). It is highly likely that MS is caused by and influenced by a complex interrelationship between these and other factors, some of which may be currently unknown.
Chapter 5: “How can nerve regeneration help?”
Once considered impossible due to the vast complexity of the CNS, the idea of nerve regeneration is now being approached through biotechnological methods like stem cell therapy. If any lasting nerve regeneration can be achieved, damage caused by autoimmune diseases like MS can potentially be reversed and people with these diseases can lead more active lifestyles. Even if these newly formed nerves from nerve regeneration are damaged again by MS, studies of this process may help to further define how MS functions and can possibly point scientists to its cause.
Possibly one of the more exciting and controversial areas of nerve regeneration biotechnology is stem cell therapy. Stem cells have the potential to replace any kind of cell in the body and can theoretically form any bodily organ that needs to be replaced which could technically revolutionize the treatment of countless numbers of diseases. Before approaching this therapy, it is important to understand what stem cells are and the differences between the different types and how they‘re procured.
Chapter 6: “What are stem cells?”
Stem cells are progenitor cells that are present from the time of conception that can differentiate into other types of cells. Not only are they the cells that differentiate to become every cell in the body during embryonic development they also act as the body’s natural repair system and can take the place of other cells that die throughout an organism’s life cycle.
Throughout its life cycle, an organism will possess three different types of stem cells, two of which only occur during early embryonic stages. These stem cells are known as totipotent, pluripotent, and multipotent. Each of these different types of stem cell has a different potential for bodily regeneration. When an embryo is less than four days old (a ball of cells known as a blastomere), its cells are referred to as totipotent, meaning that each of its cells has total potential, or the potential to become another complete human being if separated from the embryo and individually implanted into a woman’s uterus. An embryo’s cells are referred to as pluripotent when it is four or five days old. This means that although they have the potential to make up basically any cell in the three germs layers of the embryo (the embryo’s body) or to create organs, they no longer have the capability of forming another complete human being. As cell differentiation continues, stem cells are referred to as multipotent (or unipotent), meaning that although they no longer have the potential to form an entire human being, or an organ, they are still capable of forming several different types of cells. These stem cells are the kind that serve as the body’s natural repair system. In addition to being classified as totipotent, pluripotent, and multipotent, stem cells are also classified by their sources. Namely, whether or not they are adult or embryonic stem cells (National MS Society).
Adult stem cells are mostly multipotent and can be found within differentiated cells of specific tissues in both adults and young adults as well as in the placenta and umbilical cord after birth. Currently, these cells are being used to treat over one hundred different diseases due to the fact that they still retain the ability to become several different types of cells. Donating, collecting, and storing adult stem cells is a widely accepted practice and has led to the formation of a national bank for umbilical cord tissue, similar to blood banks, in order to provide more access to adult stem cells for the purposes of therapy and research Embryonic stem cells are either totipotent or pluripotent stems cells that are found in blastocysts and have a far greater ability to form other cells and possibly organs when used in scientific research. However in order to produce these cells in laboratory conditions, blastocysts must be destroyed. Therein, lies the ethical debate behind stem cell usage.
Chapter 7: “Why is there an ethical debate over stem cells?”
The debate over stem cells is centered around how stem cell research procures embryonic stem cells. Some people feel that because blastocysts are at such an early stage of development they cannot possibly have any type of feelings and thus they are not human beings. So, in their opinions it is acceptable to destroy blastocysts that are left over from invitro fertility therapy as long as they are being used to develop new medical technologies that can alleviate human suffering. However, there are others that feel that using blastocysts for stem cell research is in essence using a developing human being for unnatural purposes, similar to cloning. This group of people also hold the belief that blastocysts are human beings with full human rights and thus it is not morally ethical to experiment with them. In MS research, it is not embryonic stem cells but adult stem cells that are being studied, so the ethical debate is avoidable in this case.
Chapter 8: “What has adult stem cell research shown regarding MS?”
Due to federal regulations and the cutting edge nature of current MS treatments, there has not been a vast amount of experimentation actually using stem cell therapy with human patients. There have been, however, many experiments involving animals with laboratory designed diseases similar to MS that show the potential for a possible cure for MS.
Researchers at the New York School of Medicine have been able to extract pluripotent cells from the bone marrow of adult mice (National Institutes of Health). Because mice and humans have many genetic similarities, this could mean that mature human beings may still possess some pluripotent cells. This may means that more areas of the body could potentially be repaired using an individual’s own stem cells. For individuals with MS this could result in repairing lesions in the brain and spinal cord as well as repairing muscles that have become atrophied due to paralysis causes by MS.
Moreover, stem cells have been successfully harvested from cells lining the inside of the human nose (the olfactory mucosa) that can, in certain chemical environments, rapidly develop into several different types of cells (Nature). This makes them very similar to embryonic stem cells except for the fact that they can be obtained from any mature human being. Because the cells would be from a patient’s own body, this procedure reduces the risks of immunogenic rejection. Since MS is an autoimmune disease, people with it have a generally weaker immune system than those who do not have the disease putting them at a higher risk for rejection of foreign tissue. In many cases this therapy could be performed through injections which reduces a patient’s chance of infection. However, in some instances surgery would be necessary in order to place the stem cells in specific locations/organs of the body. Developing a stem cell therapy that does not include the risk of immunogenic rejection would greatly help to successfully implement this new technology with a higher success rate in more patients.
Chapter 9: “Are there any risks associated with stem cell therapy?”
As with any type of medical treatment there are risks associated with stem cell therapy. For example, stem cells that have been stimulated artificially to grow and divide could have the potential to go on dividing endlessly like cancer cells. These dividing cells could possibly interfere with normal bodily functions in the area(s) in which they are implanted by forming benign tumors, cysts, or even cancers at a later time.
There is also a chance that if a patient underwent a person-to-person stem cell transplant, the transplant could carry infections from the donor. However, this would more likely be due to human error. If stem cells are properly screened, like blood used in transfusions, most infections would likely be found and the risk of developing an infection would be significantly reduced.
In diseases like MS there is always a risk that even if damaged cells are able to be replaced with healthy functioning ones, and nothing is done to stop the course of the disease, the new cells may become damaged or destroyed in the event of an exacerbation. Nevertheless, many individuals with MS would most likely take this risk in order to enjoy better health. Even if the new cells were in fact damaged or destroyed in an exacerbation, studies of this process could help to further scientific knowledge of how MS attacks neurons. For example, it could help scientists to find the genetic “switches” that turn CNS repair on and off. If these “switches” are found, then theoretically gene therapy could be used to signal cells to activate CNS repair. This could in turn help to aid in the study of how myelin production and regeneration works. If more is known about how myelin is made in the CNS then perhaps we will better be able to understand how it can be regenerated and if this happens then perhaps a better method of treatment can be found. There are risks involved in this proposed in this proposed treatment. If repair cells are artificially activated, this could negatively affect the way the cells perform repairs and their interactions with other cells. Careful study of potential dangers and side effects must be investigated prior to actual patient treatment.
Chapter 10: Conclusion
This is an exciting time for MS research. Although much of the work being done currently is more theoretical than practical the fact is that the majority of experiments being conducted use animal test subjects. The information found by scientists is laying the groundwork for more in depth human studies. This is especially evident in stem cell research.
For over thirty years, adult stem cells have been used to treat cancer patients with conditions like lymphoma and leukemia through adult stem cell bone marrow transplants. Approximately twenty years ago, adult stem cells were able to be harvested from blood samples instead of bone marrow. However, it has only been within the last ten years or so that the field of stem cell research has skyrocketed. It has been studied and applied to many different fields of medical practice like cardiology, neurology, genetics, and immunology just to name a few (National Institutes of Health).
Stem cell research has especially helped to broaden our understanding of multiple sclerosis. Thanks to laboratory stem cell research we now know that lesions in the brain and spinal cord can potentially be repaired and that this repair can begin as early as one day after stem cells have been implanted in lab animals. Additionally, research has shown that the brain recruits its own progenitor cells (adult stem cells) during periods of remission that help to remyelinate axons at least on the periphery of lesions. And, we now know that stem cells can be harvested from different areas of the body and engineered to become many different types of cells. Specifically, MS patients’ cells like oligodendrocytes can be produced. This would greatly aid in reducing lesions caused by MS in the brain and spinal cord. On its present course, this research will lead to great advances in MS treatment in the not too distant future.
Advances in this field must also be looked at in a humanitarian manner. If an effective and safe means of combating MS or, at least the neurological problems associated with MS, can be found it will have the potential to change tens of thousands of people’s lives and perhaps even hundreds of thousands. Not only will more effective treatment options be able to influence the lives of people with MS, it will also influence the lives of their friends and family members many of whom are primary caregivers of the MS patient. So it is important that goals oriented towards MS research not just be for the sake of furthering science but for the sake of helping those affected by the disease.
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