Should Stem Cells Be Used To Treat Human Diseases?

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1 SAMPLE ESSAY C Should Stem Cells Be Used To Treat Human Diseases? Stem cells can be defined as undifferentiated cells that are generated during the development of the embryo. There are two functions ascribed to all stem cells, that is their self-renewal and multipotent capability. Self-renewal describes the stem cell's ability to maintain the number of cells in a given compartment constant or to increase it, in certain situations. 1 During the development of the embryo, stem cells proliferate and their progeny undergo a process of progressive lineage restriction to finally generate the terminally differentiated cells that will form mature tissues. Soon after birth, many tissues in the adult undergo physiological turnover and repair and so there is a constant requirement for a population of relatively flexible stem cells. Applications for the use of stem cell therapy have been proposed for many inherited and acquired diseases, however the isolation of human stem cells from embryos and foetal primordial germ cells in 1998 immediately prompted an ongoing ethical debate regarding the use of human embryos. 2 Stem cells can be extracted from both human embryonic cells and adult cells, the former giving rise to much of the public debate. Human embryonic stem cells (ES) are isolated from early embryos in vitro, more specifically from the inner cell mass of a blastocyst. There are three ways in which an embryo may be obtained. Firstly, they may be donated for research by patients undergoing in vitro fertilisation (IVF) treatment, these are considered to be spare embryos. The second category are research embryos, made so by fertilising donated oocytes in vitro and the third category are embryos made for research by transfer of somatic nuclei to donated oocytes 3 (somatic cells are non sex cells e.g. skin cells). The principal problem associated with this technique is the short-term culturing of human embryos to the blastocyst stage development before harvesting ES cells, particularly as the ban on embryo research has been lifted. 4 There are of course many perceived advantages in using ES, primarily due to the totipotent nature deeming them capable of forming any organ tissue of the body. Under appropriate conditions, ES have the capacity for unlimited replication while

2 maintaining totipotency, and when re-implanted into a blastocyst, such cultured ES can contribute to all the organs of the resulting adult animal. 5 Furthermore, cultured ES can differentiate into a wide variety of cell types in vitro, including haematopoietic cells, skeletal and cardiac monocytes and adipocytes. The differentiation of such cells into 'different types of homogenous precursor populations' 5 gives hope in the treatment of a variety of diseases requiring tissue repair or reconstitution, such as stroke, neurodegenerative disorders, myocardial infarction and hepatic failure. Evan Y Snyder, an assistant professor of neurology at the Harvard medical school, cloned a human embryonic neural stem cell (ENS) from a foetal forebrain. 6 These cells have the potential to be used for therapeutic grafting into adult in the treatment of a variety of neurogenetic defects, including Tay-sachs disease, birth related oxygen deprivation, spinal cord, injuries, and brain turn ours. Snyder and his colleagues removed cells from deep within the forebrain of an aborted foetus, cloned the ENS cells and grafted the immature stem cells into different parts of the developing mouse brain. The ENS migrated along existing developmental pathways and was found to mature into neural and glial cells. The ENS cells appear to correct the underlying Tay- Sachs deficiency, offering the hope that other cerebral disorders may be treated in this fashion. Human embryos used in such experimentation can only be identified and cultured after an embryo has developed for a few cell divisions. A technician must isolate and indicate an embryo prior to removing the pluripotent ES cells from the inner cell mass of the blastocyst. The culture and subsequent destruction of a human blastocyst is a matter of heated debate amongst much of the public and scientific connnunity. Peter Latchman, the president of the medical sciences in London argues, "If any somatic cell has the potential of being grown into a human being, it would logically mean that that we should ascribe a moral status to every cell in the body - a concept that is clearly ridiculous". 7 However, many believe that gametes and gene may be treated as incomplete commodities (i.e. non human beings), but whole genomes, zygotes and embryos should not be sold on the research market. The blastocyst contains a complete genome and all that is needed to develop it into a human being. It is clear that the ethical justification for sustaining the lives of human embryos in vitro for the express purpose of harvesting Es cells has not been provided and requires a clear definition of moral and legal status of human embryos.

3 Despite the huge excitement surrounding the technical breakthrough, stem cell therapy is still in its infancy and is considered a novel treatment commodity. Even though scientists have been working with embryonic stem cells for many years, they will still need to create scores of embryos to generate a single line of usable cells. In humans, this would be largely unaffordable. In Britain alone, there are 120,000 patients with Parkinson's disease and 200,000 with juvenile Diabetes. Therapeutic cloning would require up to 30 million eggs. Yet a woman cannot donate more than a dozen eggs a month and this is often an unpleasant and risky procedure, involving daily injections of powerful hormones followed by surgery. On average, each of these women are offered payments of $4000, these costs would have to be covered by recipients of embryonic stem cell therapy. As a result, the technique would be largely restricted to rich countries and rich people. The ethical issues surrounding human embryonic stem cells has stimulated research into alternative ways of generating required tissues. One option is the use of adult stem cells. This involves harvesting organ-specific stem cells from a particular organ; the cell is expanded in vitro and re-implanted into the patient. The usefulness of this kind of stem cell transplantation has been limited by the fact that many organ; including the brain, spinal cord, heart and kidney, were thought to lack detectable stem cells. It was also believed that cells from these organs could not be reprogrammed to differentiate into different cell lineage during adulthood. However, recent discoveries have revolutionised adult stem cell biology and have demonstrated the clinical potential of these cells in a wide range of human diseases. First, stem cells have been detected in organs previously thought to lack regenerative potential. For example, several areas of the brain contain stem cells that maintain the ability to proliferate and mature into different types of neural cell, both in vivo and in vitro. Similarly, studies have shown that skeletal muscle stem cell (myoblast) can be cultured in vitro and transplanted into patient's muscle where they differentiate into myotubes and fuse with endogenous muscle fibres, enabling the recipient to regain lost muscular function. Second, organ-specific adult stem cells appear to display much more plasticity than originally thought. Until recently, the consensus was that the differentiation potential of adult stem cells is restricted to generating exclusively the different cell types found in their residing tissue. However, recent animal experiments have shown neural stem

4 cells do differentiate into haematopoietic lineages. 8 Stem cells derived from bone marrow can differentiate into several non-haematopoietic lineages, including skeletal muscle, microglia and astroglia in the brain and hepatocytes. These findings raise the exciting possibility of using bone marrow transplantation to treat a wide variety of disorders, such as muscular dystrophies, Parkinson's disease, stroke and hepatic failure. One of the most remarkable demonstrations of cell plasticity has come from animal cloning experiments. In 1997, Dolly the sheep was cloned by transferring a mammary gland cell nucleus into an oocyte 9. Similar techniques have been used to clone mice, cows and monkeys, demonstrating that mature stem cells can be reprogrammed to totipotency. This would allow the generation of specific types of therapeutic stem cell in vitro from only a small number of differentiated cells from the patients (e.g. a skin or muscle biopsy), avoiding immune responses to the transplanted cell. Like many novel therapeutic approaches, stem cell therapy raises a number of difficult important ethical issues and concerns. Many reviews have been concluded that obtaining human embryonic stem cells from aborted foetuses or surplus embryos of in vitro fertilisation are unacceptable from an ethical standpoint. 4 It is sad that there is now serious requirements for a clear definition of the moral and legal status of human embryos but it is true to say that this issue was initiated not by stem cell therapy but by abortion and in vitro fertilisation. It is clear that many of the benefits associated with ES are also exhibited by adult stem cells, the use of which would not give rise to such heated debate. In addition, the supply of adult stem cells would not be limited, which would lower the cost of such therapy. References: 1. Gritti A, et al. (2002). Adult neutral stem cells: plasticity and development potential. Journal of physiology. Vol 96; pg Ryan K (2000). The politics and ethics of human embryo and stem cell research. Womens health issues. Vol 10. No 3; pg McLaren A. (2000). Important differences of sources of embryonic stem cells. Nature. Vol. 408; pg Meyer J. (2002). Human embryonic stem cells and respect for life. Journal of medical ethics. Vol 285; pg

5 5. Kaji E. (2001). Gene and stem cells therapies. Journal of American medical association (JAMA). Vol 285; pg Flax JD et al. (1998). Engrafatable human neural stem cells respond to development cues, replace neurons and express foreign genes. Nature biotechnology. Vol 16; pg Latchman P. (2001). Stem cell research- why is it regarded as a threat? EMBO report. Vol 2; pg Bjornson CR et al. (1999). Turning brain into blood: a haematopoietic fate adopted by adult stem cells in vivo. Science. V 01283; pg Resnik D. (1998). The comodification of human reproductive materials. Journal of medical ethics. Vol 24; pg