The future use of stem cells in treating diseases such as alzheimer’s and diabates

THE FUTURE USE OF STEM CELLS IN TREATING DISEASES Grade awarded June 2006: PASS WITH DISTINCTION Following on from an introduction to stem cell research at “Medlink 2005”, this paper will continue to investigate this branch of modern technology. It will explore the various ways in which it can be used in medicine to find solutions for biological problems which have, up until now, been deemed “unsolvable”. In this research paper, we will first describe the background and principles of stem cell technology, its’ current uses and some of its’ possible applications to modern medicine. We will then discuss how this technology could be developed and implanted into the body to cure diabetes and Alzheimer’s. In addition we will look at the ethical concerns that could arise following new developments before concluding with our thoughts on whether there is a possibility of stem cell technology becoming common practice. Introduction Stem cells (in animals) are that keep the and er cell types(1). The main types are: adult stem cells and embryonic stem cells. Adult stem cells are undifferentiated, somatic cells found among differentiated cells of a specific tissue and are said to be multipotent. Multipotent stem cells are limited to different types of cells they can turn into, an example being hematopoietic stem cells that are restricted to differentiating into other blood cells (19). In the body such stem cells are responsible for making red and white blood Adult stem cells are already being used in treatments, showing particular success in inherited blood disorders such as leukaemia and lymphoma. Adult stem cells can be found in the blood, bone marrow, skin, brain, liver, fat, placenta, umbilical cord and amniotic fluid. Adult stem cells termed sues and survive long time periods and harsh conditions(2). Finding and removing adult stem cells can be done with relative ease and does not affect the person from which they’re withdrawn(3). the undifferentiated inner mass cells of an early st. They differ from adult stem cells as they are pluripotent. Pluripotent cells are capable of affecting more than one organ or tissue and can therefore develop into any type of cell by cultivation in stem cell lines. These cells are unique because at early stages in development they are not specialized and have the capacity to develop into 130 different human tissue types(6). Thus embryonic stem cell research is thought to have much greater development potential than adult stem cells. However current understandings of the nature of embryonic stem cells is limited and perhaps further research should occur before the application of these cells becomes widely practiced. The research into embryonic stem cells has caused great controversy because in order to start a stem cell line in which these cells can be cultivated, a human embryo needs to be destroyed, or cloned. This creates religious and ethical implications which need to be addressed if embryonic stem cells are to be applied in modern medicine. We shall reason our thoughts on these ethical issues when concluding this investigation. There are also cord red blood cells. These are derived from the blood of the after birth. Since 1988 these ce “Cord blood banks” have been created whereby stem cells are collected by detaching the umbilical cord, sterilising it and withdrawing blood from the umbilical vein. This blood is then analysed for possible disease-causing substances and can be injected into the body via a vein at a later date. This treatment which uses stem cells collected from another donor is called “allogeneic” treatment. Treatment whereby the cells are collected from the same patient on whom they will be used is called “autologous”, and when collected from genetically identical individuals such as twins, it is referred to as “syngeneic”(4) . Many research scientists believe that this technology will lead to therapies for some degenerative diseases such as diabetes, Alzheimer's and heart disease but this depends on people’s acceptance to the techniques used. To alleviate people’s fears of stem cell technology, the argument could be made that bone marrow transplants and umbilical cord blood transfusions have worked very successfully for years, and stem cell therapy uses exactly the same principles(5). The trans-differential nature of embryonic stem cells as described previously creates possibilities to cure degenerative diseases by replacing damaged somatic cells with new cells. Examples of such diseases include Parkinson’s, osteoarthiritis and coronary heart disease. However the application of stem cell technology to diseases such as diabetes and Alzheimer’s is not so widely accepted. The future of stem cell technology in these two diseases has opposing outlooks and through this discussion we shall identify possible areas where stem cell therapy may or may not have benefits. Firstly, we will look at Alzheimer’s. This disease is “a progressive form of presenile dementia that is similar to senile dementia except that it usually starts in the 40s or 50s” (7). The symptoms start with impaired memory and thought, leading to difficulties in communicating and finally complete helplessness. It involves the gradual deterioration of sensitivity of the motor and relay neurones existing in the brain. Nerve cells die in a random way, interrupting the complex inter-connections of nerve cells in the cortex. It is this network of cells that facilitates our memories, personalities and behaviour patterns(8). At present there are no drug treatments which provide a cure for the disease. Drugs such as Aricept, Exelon, Reminyl and newly developed Ebixa can temporarily slow down the progression of symptoms in some people but have not shown a promising cure(9). These drugs help to maintain levels of Acetylcholine which acts as a neurotransmitter between neural synapses. As such Acetylcholine is very important in communication through electrical signalling between nerve cells. To ensure the control over this communication, and that preceding impulses are able to cross the synapse, an enzyme called acetylcholinesterase breaks down acetylcholine at the synaptic cleft(14). In Alzheimer’s sufferers this enzyme is produced by the neurones at a higher rate than acetylcholine. As such the concentration of acetylcholine is being constantly reduced until levels of this neurotransmitter are so low that the electrical signals can’t cross the synapse. The drugs mentioned above act as inhibitors to acetylcholinesterase or, such as Reminyl, they act on the nicotinic neuronal receptors making them release more acetylcholine. In non-Alzheimer’s sufferers, adult stem cells travel from the bone marrow to become fully functioning brain cells and so help to replenish and replace deteriorating nerve cells. However in Alzheimer’s sufferers this process does not occur at a sufficient rate and so the problems of signalling through nerve cells is worsened. The use of stem cell therapy could correct these problems. Embryonic stem cells may have a use as they could be injected into the veins of the cerebral cortex located precisely in the region where the majority of nerve cells exist. They would then develop into the nerve cells in the surrounding tissues, regenerating whole regions of nerve cells and thus building replacement neural tissue. The number of healthy neurones would increase, so more acetylcholine would be produced. Depending on the success of such therapy the drugs mentioned above may no longer have a use. If the levels of acetylcholine were still not quite sufficient then combined use with the drugs would allow communication between synapses to temporarily increase. Furthermore, the increased production of acetylcholine in the brain will allow signals to flow and reduce brain-cell damage if the disease is treated early. Less brain-cell damage lowers the production of the neurotransmitter, glutamate, which is released in excessive amounts when brain cells are damaged by Alzheimer's disease to try and improve cell to cell signalling. In excessive amounts glutamate causes further brain damage. The result of such stem cell therapy would also reduce the damage caused to the brain in early stage Alzheimer’s without the use of Ebixa which has a similar effect. However, this treatment would require a need for constant injections of embryonic stem cells into the brain in order to replenish the depleted state of the nerve cells. At present this could lead to fatal complications as continued success is not guaranteed. Further research and evidence must be produced to conclude that stem cell therapy would at least reduce the effects of Alzheimer’s. Also, due to the loss of many different types of nerve cells in the brain and the impact that the disease has on communication between cells, developing stem cell therapy for Alzheimer’s disease would be more complicated and challenging than it appears in theory. Additionally, it is not just further research into stem cells which will be needed as the precise cause of Alzheimer’s is unknown. As two researchers told a U.S. Senate subcommittee in May 2005, Alzheimer’s is a "whole brain disease," rather than a specific cellular disorder (such as Parkinson's). Stem cell experts thus confess that of all the diseases that may be someday cured by embryonic stem cell treatments, Alzheimer's is among the least likely to benefit(11). The future use of stem cells for curing diabetes looks more promising. Diabetes is fast becoming a more concerning condition than ever before. Currently this disease affects 5% of the world’s population and its prevalence is doubling every generation and as such the number diagnosed with diabetes is predicted to rise from 2 million to 3 million by 2010 in the UK alone(12). It is primarily thought that this is a result of higher life expectancies with increasingly inactive lifestyles. It is important when addressing possible developments towards cures for diabetes that the two types of diabetes are considered individually. Type 1 diabetes, also known as insulin-dependent diabetes, is a disease that destroys the cells in the pancreas that produce the hormone insulin. Sufferers are unable to produce insulin at all. They rely on boosting their insulin levels by regular injections or wearing a pump that distributes the hormone under the skin. These injections are impractical and can be fatal if missed. Use of the pump and injecting insulin repeatedly into the same part of the body can cause lipodystrophy. Two types of changes can occur: lipoatrophy and hypertrophy. Lipoatrophy involves an immune reaction to the insulin that is injected at the sites. It causes concavity or the disappearance of the fatty tissue under the skin at the injection site. This creates unsightly areas of tissue that appear to be hollowed out. Although this problem was more common when less purified animal insulin was administered, human insulin currently used sometimes have such an affect. Hypertrophy is a build-up of fatty tissue at the injection site whereby the accumulation of fat cells can create a lumpy appearance in the skin. Type 2 diabetes, or non-insulin dependent diabetes, is where sufferers do make insulin but not enough or are unable to make full use of it. Due to the undesirable affects outlined above and the lack of normality that such ‘solutions’ offer to sufferers, further stem cell research and the development into more permanent and practical cures has been initiated. Current areas of research are targeted at the use of animal stem cells. These could be programmed to grow into islets. Islets are clusters of cells in the pancreas responsible for producing insulin as well as glucagons, and pancreatic polypeptide. There are five types of cells in an islet: beta cells, alpha cells, delta cells, PP cells, and D1 cells. Some success has been seen through islet cell transplantations whereby these clusters have been taken from dead donors. However such cells are often damaged and as a result their success is hampered. In addition a single donor pancreas only provides about 250,000 to 500,000 islets. Each recipient patient, however, needs about 800,000 cells before he or she is ‘insulin free’. Consequently, the patient normally needs two infusions of the cell clusters, from two donors. The negative result is that if success is secured on islet transplants and if such protocol becomes more common-place, the demand on an already short supply of donor organs will inevitably increase dramatically. Recent development has seen success of islet transplantation from living donors and within recent months a 61 year old man became the first Type 1 diabetes sufferer in the UK to be cured(13). Obtaining islets from living donors yields greater success as there is often greater acceptance of the cells and their function is accordingly retained. Donor cells from family relations reduce this risk of rejection even more. Further advantages include greater number of possible donors compared to islets obtained from deceased donors as just half a pancreas from a living donor, compared to two from the deceased, bears the islets needed for transplantation. After being injected into the recipient’s liver(14) they develop their own blood supply and begin to produce insulin. However use of islet cells from living donors has still not produced conclusive results to confirm such use of stem cells is the possible future cure for diabetes. Other transplantations have been attempted but were unsuccessful and recipients are still subject to powerful drugs to ensure the new cells are not rejected and attacked by the immune response system, many of which have objectionable side effects. Further risks include the donor receiving an increased threat of diabetes and the considerable danger of the surgery involved. Further fields of possible answers to Type 1 diabetes through stem cell research has been explored by U.S scientists. This began by considering the use of embryonic stem cells being programmed to resemble insulin producing islet cells. Preliminary research showed that such cells can turn cancerous and have other unpredictable effects. On closer study of islet cells it was realised that islet cells resemble neurons and that in some insects, such as fruit flies, the insulin producing cells are neurons. This proposed possible advances in taking stem cells from the brain. By adding a developed mixture of chemicals to brain stem cells of an aborted foetus it was found that the cells changed. Although this change did not produce cells identical to islet cells, they did produce insulin in response to raised blood sugar levels. Initial tests were carried out by inserting these cells into kidney’s of mice and the desired responses were seen with no cells becoming cancerous. Conclusion The two diseases discussed show the contrasting benefits and implications of stem cell therapy in medicine. It seems that in the case of Alzheimer’s, and other forms of dementia, stem cells do not currently hold the cure for sufferers but can only reduce the decline and damage to the brain. Nevertheless scientists still hold hope and in 2002, the Alzheimer’s Society awarded a fellowship grant to a three-year research project entitled ‘Neural Stem Cells and Replacement of Lost Neurones in Experimental Models of Neurodegeneration’(9). Its aims are to develop nerve cells from bone marrow stem cells through extensive study with animals. The future of stem cell therapy for Diabetes is much more promising. Although tests are still to be carried out on human patients, the initial results from animal testing have been very promising and scientists say that further developments could free Type 1 diabetics from insulin injections and pumps. This work underlines the potential that stem cell research has for curing an increasingly prevalent disease such as diabetes. As this discussion has shown, stem cells may hold the key for a number of degenerative diseases but there are a number of ethical and social hurdles that will have to be overcome before stem cells can truly be applied in modern medicine. As such, ‘Advanced Cell Technology’ assembled a board of outside ethicists to weigh the moral implications of therapeutic cloning research(15). Considerable debate has been raised on the level of respect and sanctity that should surround the embryos destroyed to obtain embryonic stem cells. A scientific viewpoint is that when the embryonic stem cells are obtained they possess no human characteristics, cannot possibly feel or think and are just simply a small bundle of cells. As such scientists use the term ‘activated egg’. However in the religious teachings of Catholic Christians it is stated; ‘From the time that the egg is fertilised, a life has begun’(16). Therefore some Catholics believe that as the embryo destroyed could possibly develop into a human being, these ‘activated eggs’ possess the same sanctity of life as a developing foetus. Protestant teachings states ‘early embryos do not have the moral value of persons’(17) and thus most Protestants do not have ethical objections to embryonic stem cells. Despite acceptance of stem cell therapy by some religious groups, scientists must act with sensitivity regarding future developments as many people believe this research will lead to human cloning. Such practice is highly objected to by most of society and will always continue to be ethically wrong. Other disagreements surround the procedure to obtain human eggs which subjects the donating woman to stimulatory medications that can develop liver damage, kidney failure or stroke(15). Also an increased risk of ovarian cancer raises moral issues as to whether subjecting women to these risks for research is justified. With so many moral and ethical issues surrounding embryonic stem cells, it follows that adult stem cells may offer the future for socially accepted stem cell therapy. However their multipotency characteristics limit their use in modern medicine. With the research we have done for this investigation we believe that funding should be injected into experimenting with other techniques of obtaining embryonic stem cells by extraction, which doesn’t involve cloning or the destruction of a human embryo. Alternatively concentration could be put into developing the research of obtaining pluripotent cells from multipotent cells(18). Such development would remove the ethical and moral issues that are restricting the impact that stem cell therapy is having on modern medicine and could lead to future cures. References (1) (2) (3) (4) (5) (6) (7) (8) (9) (10) (12)Diabetes in the UK 2004, Diabetes UK October 2004. (13) http://news.bbc.co.uk/1/hi/health/4330717.stm (14) (15)(16) Catholic declaration on abortion ’74 (17) Lord Habgood, former Archbishop of York (18)(19) http://en.wikipedia.org/wiki/Hematopoietic

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