Stem Cells-The Future of Medicine?

Transcription

1 Stem Cells-The Future of Medicine? By Dominic Rushton Pass with Merit Research Paper based on Pathology lectures at Medlink

2 This paper will be on the topic of stem cells, and the research and development of treatments, as well as other regions of this enthusing area of medicine. I will be highlighting different treatments, the research behind these treatments from different scientific bodies, and ultimately the moralistic issues regarding the use and application of stem cells, especially embryonic. The research for this paper comes from many different scientific sources, including the internet, and documents accounting research into different methods and applications of stem cells. My conclusion, that I will go into further detail at the end of the paper, is that stem cells are the future in terms of different treatments available for certain diseases, this use needs to be regulated heavily however, with research into them being completely reliable. Stem cell research is definitely one of the most exciting areas of medicine at this present time, as well as all of science. It seems to promise, with further research, the ability to repair and self-renew damaged cells, without the fear of rejection and the taking of antirejection drugs, which often cause further damage to the organs of the body, as genetically identical cells are produced. They promise to change the face of human disease, and ease the suffering of many people living with illnesses such as Parkinson s disease, diabetes and Alzheimer s. The amount of lives that could be saved via the use of this treatment is unimaginable, and would save large amounts of money for the NHS for the treatments of chronically ill patients, as well as improving their quality of life. At this juncture, this is only a dream, but the idea that our bodies can simply be repaired with the injection of unspecialised cells is an incredibly attractive prospect, although at this stage, is not possible. This practice is still in very early stage of its life cycle, but already advances are being made in treatments and procedures for certain illnesses, with stem cells often at the forefront of these. A number of stem cell therapies currently exist, but are extremely costly and experimental; the most notable exception is bone marrow transplantation. A total of 50,417 first bone marrow stem cell transplants were reported as taking place worldwide in 2006, to treat severe disabling auto immune diseases and cardiovascular disease. This method of treatment introduces stem cells that are present within the bone marrow (Figure 1), which can differentiate (alter their structure into the structure of a specialized cell) to provide the recipient with cells that they may perhaps be deficient in, for example red blood cells for patient with sickle cell anemia. The discovery for the use of stem cells was pioneered by a team led by E. Donnall Thomas, whose work was later recognized with a Nobel Prize in medicine. Thomas work has been incredibly important, as it illustrated that bone marrow cells could repopulate bone marrow and produced new (red) blood cells. 2

3 This diagram illustrates the huge range of specialised cells that stem cells from human bone marrow can differentiate into in order to treat diseases within an individual. For example the production of cells that fashion the cardiac muscle, for the treatment of cardiomyopathy (Figure 1) Ethical issues surrounding stem cell research is rich with emotion, especially regarding the use of embryonic stem cells since their discovery in 1998, which are recovered from unborn embryos before they have chance to develop. This brings up many issues regarding the potential life that has been ended, especially from religious organisations, where their sanctity of life has been violated, in their opinion. They are obtained by fertilizing an egg outside of the womb (in vitro fertilization), and are taken a few days after fertilization, where the embryo has developed into a stem cell rich blastocyst. Embryonic stem cells are used due to their pluripotency (their ability to differentiate into almost every type of bodily cell), as well as their ability to replicate for an indefinite period. The different types of stem cells, as well as their usefulness and application will be explained further in the paper. 3

4 Stem cells are undifferentiated cells that exist in the bone marrow, liver and brain of adults, but occur most abundantly in embryonic samples, such as in a blastocyst. There are two different types of stem cells, pluripotent and totipotent. The main difference between these two types of cell in regards to their importance in stem cell research is what they can produce. Totipotent stem cells can divide to produce further stem cells (Figure 2); they are present in embryos, and produce the pluripotent stem cells that are used in different stem cell therapies. Totipotent cells can produce the entire organism, whilst pluripotent cells differentiate to produce certain specialized cells, in the case of an embryo. Totipotent stem cells are not found in adult bone marrow, or other such places where stem cells exist. They are called Somatic stem cells and are located in small quantities, throughout the body and generate specialized cells for the area they are located. These cells do not renew themselves as well as embryonic stem cells, and are therefore less useful for research and treatments. For example there are a relatively small number of stem cells located in the brain, which differentiate to produce neurons throughout a person s life. A dream that many scientists and biologists share is the ability to harness the stem cell producing power of a totipotent stem cell. This would enable large amounts of pluripotent stem cells to be made, and reduce the amount of foetuses used for embryonic stem cell research. At this stage foetuses are developed a little while longer, and only pluripotent stem cells are taken. There are several different pathways scientists and medical professionals are taking with stem cells, as the ability to regenerate lost tissue and even organs (this is the dream) is an idea that they can t afford to overlook. A new potential method for the production of pluripotent stem cells was published in a scientific journal on August 23 rd 2006, where a group of scientists working on stem cells, claimed to have discovered a way of producing pluripotent stem cells from already differentiated, specialized 4

5 cells. This would prevent the destruction of embryos, as pluripotent (which are sought after in embryonic stem cells) cells would be able to be extracted. This would assist stem cell research greatly, as ethical protests against the practice will be increasingly subdued. These ethical issues regarding the destruction of an embryo led to stem cell research funding to be cut in 2001, although this limitation was lifted in 2009, the ability to gain stem cells without the destruction of potential life would certainly gain more support for the practice, whether it be financial or morale. This research was headed by Dr. Robert Lanza, who claimed that pluripotent stem cells, highly similar to those found in embryos, can be generated using the application of three genes, to differentiated cells. These genes act as re-programmers, transforming differentiated cells into their original pluripotent cells, allowing for the production of pluripotent stem cells without the need for an embryo and the taking of potential life. It is believed that this method, rather than that used on embryos, will be less controversial to members of the scientific community, and the public alike. This method of producing pluripotent stem cells has already begun it s testing on mice, where mouse pluripotent stem cells were confirmed to be produced. The dream is that this therapy can produce patient specific pluripotent stem cells, which could potentially be used for cell replacement therapies. Take Alzheimer s or Parkinson s disease as examples. These two illnesses could be treated, with the use of genes, to un-differentiate cells such as neurons in the patient s brain. These pluripotent cells would then divide, and differentiate back into neurons, where they then are used in the brain. This has not been the only situation where pluripotent stem cells have been attempted to be induced in the body Rudolf Jaenisch, of the Whitehead Institute for Biomedical Research in Cambridge Massachusetts, documented that used induced pluripotent stem cell technology to cure mice of sickle cell anemia, by producing new red blood cells from created pluripotent stem cells. A California based company called Stemagen, announced in 2008 that they had created the first mature colony of human embryonic stem cells from a single skin cell taken from an adult. These stem cells can be harvested for matching patients to these cells. Stem cell therapies are not only moving forward because of what they can accomplish in terms of treatment, they are also moving away from embryonic stem cells, and a large amount is being invested into research and development of producing stem cells by other means. The dream is that stem cells one day, can be produced without the destruction of potential life, and in my opinion, this dream will soon become reality, with many exciting breakthroughs being made, especially through the production of stem cells from the patient s own tissue/cells. 5

6 Dr. Lanza has also recently been involved in a breakthrough regarding the treatment of blindness with stem cells. Human embryonic stem cells were used in this case. The purpose of the test was to test was so simply measure the safety of stem cells on the eye. But Dr. Lanza was quoted as saying that the patients had measurable improvement to their vision that persisted through the duration of the study. This is one of the first times that stem cells have yielded practical results for patients. One of them no longer needs a large magnifying glass to see, and has given the patients a large amount of their independence back. The cells were transplanted into the eye, an organ known for low chance of immune rejection. The stem cells injected were not required to perform a heroic act of reconstruction, and were kept under favorable conditions unlikely to exist in many diseases. However this provides hopes for many suffering, as well as useful information for the use and experimentation of stem cells in the future, regardless of how preliminary the findings are, Hopefully, this is just the beginning of many exciting new stem cell therapies that will move from bench to bedside in the next few years Dr. Lanza was quoted as saying. The first full transplant of a human organ was carried out by Paolo Macchiarini at the Hospital clinic of Barcelona. The patient, Claudia Castillo, trachea had collapsed due to a tuberculosis infection. A donation of trachea tissue was used, seeded with stem cells that were taken from the patient s bone marrow. This was grown in a laboratory for a few days, and transplanted into the patient s left bronchus. This was a huge breakthrough in stem cell usage. Due to the stem cells being harvested from the patient s own bone marrow, no anti-rejection drugs were needed. Four months on, the new trachea was showing no signs of immune rejection, a great success for stem cell treatment. 6

7 What is being done with stem cell treatment is certainly exciting. The idea of replacing old and damaged tissue with new material, genetically identical seems incredible. Stories such as Claudia Castillo s fill the scientific and medical universe with excitement and expectation. Just imagine how many people you know with diabetes, a growing problem that puts a huge strain on the National Health Service, around 3.5 billion per year. With the introduction of stem cells, with research, to produce pancreatic cells more capable of producing insulin, this figure will reduce massively, as well as improving patient s quality of life significantly. The eagerness surrounding stem cells is therefore fully understandable; I do not think too much hope should be put in it at this stage however. The production of genetically indentical piece of tissue, that saved a woman s life is incredible, however the tissue produced was basic epithelial and cartilage material. Compared to an enzyme and chemical factory such as a liver or pancreas, where the very homeostasis of a person is based, the production of a trachea is relatively meager. The possibility of producing a complex organ such as a liver, pancreas or stomach, is not too far into the future, however, a large volume of research must go into this before it becomes even a possibility. This does not mean that stem cells as a partial treatment, and not for the production of an entire organ, are not a possibility. A recent study, by researchers from Cedar-Sinai Heart Institute in Los Angeles and Johns Hopkins University in Baltimore, tested the effects of applying pluripotent stem cells to patients who had recently suffered from heart attacks, and whose tissues had been damaged by the event, with the hope that it might reduce the risk of heart failure in the patient. The trial consisted of 25 heart attack patients, 17 of which received stem cell treatment and showed a 50% reduction in cardiac scar tissue compared to no improvement to the others who received standard care. The stem cells are grown from the patient s own cardiac tissue, to prevent an immune response. It allows the cardiac tissue to heal after a heart attack, a process that was thought not possible until now. Deepak Srivastava, director of the Gladstone institute for cardiovascular disease said The findings in this paper are encouraging, there s a dire need for new therapies for people with heart failure, and hopefully stem cell related therapy is the answer. The theory behind this practice is that although the patients receive no extra improvement in heart function, the heart does receive extra strength in the way of new cardiac muscle/cells. This procedure shows that stem cells are not an all or nothing procedure, and can be used in combination with other therapies in order to improve the condition of a certain organ. 7

8 With a treatment as promising and exciting as stem cells, there are bound to be some downsides to the application and treatments involving them. The ethics surrounding stem cells are clouded in controversy, especially embryonic stem cell research, which requires the termination of an unborn embryo in order to access the pluripotent stem cells. As a result the practice receives a lot of criticism, and is banned in many countries such as Germany and France. This hatred has led to increased pressure on the scientific community to produce a different method of obtaining stem cells; one which doesn t involved the destruction of an embryo. The use of stem cells that is present in cord blood, in the placenta of recently mothers is being looked at by scientists and other medical professionals. These cells, just as embryonic stem cells, can be used to treat hematopoietic and genetic disorders, such as leukemia. The problems with this method of obtaining stem cells is that often there is only a small amount of them contained in the cord blood, certainly not enough to treat a fully grown adult patient. The baby s blood is often starved of iron when the placenta is clamped, if the process is not performed properly, causing problems for the child in the first 3 months of its life. Tests have already begun with the use of cord blood on newly diagnosed type 1 diabetic children. The results show that with the application of the stem cells found in cord blood, the rate at which insulin production is lost in the child significantly reduces. This method is only ever used with cord blood specific to that child when it was born, as the chances of rejection must be kept at a minimum in child patients. The stems cells in cord blood are showing even greater promise in regards to cardiovascular repair. The cells seem to selectively migrate and seek out damaged tissue, perhaps from a previous heart attack, and repair and strengthen the area, improving heart function as a whole. The use of cord blood as a source of stem cells may well become more and more popular in the future, as ethical issues surrounding the use of embryonic stem cells only seems to increase in intensity. Another criticism of stem cell research is the dangers to the patient it poses when it is used. Cancers can often occur when used incorrectly. The stem cells divide when they reach their target tissue, to produce a greater number of differentiated specialized cells. This is when the cancerous growth can develop. Stem cells have a greater tendency to become cancerous than other donated tissues, and many skepticisms have been raised about them for this reason. 8

9 So, in conclusion, are stem cells really the medicine of the future, the super treatment that will enable lifelong conditions such as diabetes and multiple sclerosis to be corrected? At this stage, this is simply a dream of physicians and scientists alike, but there are signs that stem cell treatment is moving forward, with therapies slowly being developed. Perhaps sometime in the future stem cells will have reached a point where incredibly complex organs like a liver can be produced, and can be transplanted to the patient without fear of immunosuppressant drugs, along with the side effects those drugs come with. Perhaps paraplegics will have their disabilities cured with a simple injection into their spinal column, or give people with lost limbs the ability to grow them back. There are many secrets yet to be unlocked about the nature and abilities of stem cells, and how they can solve many medical problems that plague many people, but for now, it is a practice in its infancy, but with time will mature to offer people long term solution to health problems they encounter. Ethical issues such as the use of embryonic stem cells are slowly being amended and other sources of stem cells being heavily researched, with breakthroughs being made. The possibilities for stem cells seems endless, especially when paired with exciting other technologies such as nanotechnology, but I do not think they are a treatment or area of science that should be entered with a cavalier attitude, and should be respected as much as the diseases they treat, as they can be just as dangerous as them. 9

10 References Audrey R. Chapman, Ph.D., Mark S. Frankel, Ph.D., Michele S. Garfinkel, Ph.D. (1999) Stem Cell Research and Applications, Monitoring the Frontiers of Biomedical Research (3-5) The use of stem cells for the treatment of patients with damage to cardiac tissue, article by San Francisco chronicle, based on research by Cedars- Sinai Heart Institute in Los Angeles and Johns Hopkins University in Baltimore: Ethical issues surrounding the use of embryonic stem cells: Stem Cell research breakthrough, blindness treated, article by San Francisco Chronicle, based on research inside stem cell paper Lancet : General information regarding stem cells derived from adult tissues: General information regarding stem cells derived from cord blood: General information regarding stem cells and stem cell research: Information regarding the treatment of Claudia Castillo, patient who had trachea built from her own stem cells, article by NewScientist: