The Potential for Stem Cell Breakthroughs Without Controversy. By Fiona Clark. Word count: Approx Grade awarded June 2006: PASS WITH MERIT

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1 The Potential for Stem Cell Breakthroughs Without Controversy By Fiona Clark Word count: Approx 2000 Grade awarded June 2006: PASS WITH MERIT Research Paper Based on Pathology Lectures Vetsix

2 ABSTRACT Recent developments of stem cell technology have opened up seemingly infinite possibilities for human and veterinary medicine in the future. However, currently, progress is hindered by ethical controversy surrounding the use of embryonic stem cells, and by the limitations of the more widely acceptable adult stem cells. My research focuses on the fast-evolving nature of the field, and the potential transferral of hope to new sources of pluripotent cells such as cord blood and, in particular, Wharton s Jelly, in finding more complete and efficient treatments of disease and injury in animals. INTRODUCTION Stem cells are undifferentiated cells, which can be stimulated within the body to replicate and to differentiate into any kind of tissue. During embryonic development, all body structures are formed from stem cells, but small supplies of undifferentiated cells remain in certain regions throughout life. These adult stem cells, whilst still versatile, are less pluripotent than their embryonic counterparts, tending to be limited in their differentiation to particular types of tissue in the immediate vicinity of their source. In 1998, a veterinary graduate and biochemist at Wisconsin University, James Thompson, successfully cultured a stem cell line from embryos discarded from fertility treatment. This had huge implications for the future of medical research, since it introduced the idea of harnessing the versatility and regenerative properties of embryonic stem cells to combat previously incurable diseases. Research teams across the globe expressed hopes to find stem cell answers to diseases such as Alzheimer s, Leukaemia and Neuroblastoma. Instead of using drugs or manmade replacements to relieve symptoms, what if the body could be prompted to heal itself on a grand scale? However, many feel that the use of material derived from aborted or discarded embryonic/ foetal humans for medicine is ethically unacceptable, and some reject therapeutic cloning, because though it does and could not produce a human, it requires the replacement of the nucleus of a human (albeit unfertilised) egg. Consequently, it could be argued that this gamete, is denied the potential to become a human. 2

3 Recently, cord blood has come to the forefront of the stem cell debate, as a viable alternative to embryonic stem cells. Cord blood is blood remaining in the umbilical cord, which can be obtained after birth with no harm to the baby, indeed thousands of parents are paying cord blood banks to store their infants samples for medical use in the future. In this blood, primitive, undifferentiated cells have been found, from which it is possible to generate cells of the nervous, blood or immune systems. Even more excitingly, Wharton s Jelly, a tissue which protects blood vessels in the umbilical cord has been found to contain 1 stem cell per 300 cells (compared to only 1 in 300 million in cord blood). Research has shown that Mesenchymal stem cells obtained in this way are a potentially inexhaustible, easily harvestable supply which can differentiate into a variety of cells, including neural cells (Mitchell et al- 2004) and (Ming-Song et al ). A research team at Kansas State university, which consisted of several veterinary biologists, stated their hope that Wharton s jelly could provide the scientific and medical research community with a non-controversial and easily attainable source of stem cells for developing treatments for Parkinson's disease, stroke, spinal cord injuries, cancers and other conditions (Weiss and Troyer 2004), as well as the possibility of stem cell use to target the delivery of therapeutic proteins. Therefore, I am proposing that stem cells acquired ethically from post-natal material be used to develop treatments for complaints commonly seen by the veterinary profession. DISCUSSION There are many cases in which the veterinary surgeon is presented with a condition which can be treated, but only clumsily, with low success rates, unpleasant side effects or superficial control of symptoms. In the case of some diseases, no cure is known. However, with the advent of ethically sound stem cell technology, surely work already pioneered using adult stem cells could be expanded indefinitely to replace older, less effective techniques. 3

4 A case in point is that of prize race or show horses. Unlike the case of the farm animal destined for the abattoir, these animals owners have the incentive, and often the money, to find the right treatment, even if that treatment is expensive or complex. Adult stem cells taken from the horse s fat are already being used to regenerate tissue in joints, as preferable to the messier formation of scar tissue, which results in lower performance levels and higher risk of re-injury, not to mention a long recovery period. With a source of stem cells so abundant as Wharton s jelly ( within three weeks, a sample of these cells can produce yield for up to 1,000 therapeutic doses), compared to the relatively sparse occurrence of adult stem cells, the availability of such treatment could become much more widespread. In addition, other problems for a race horse could potentially be combated in this way. Osteoarthritis could be targeted, by the regeneration of the cartilage and even bone material. Animals suffering from neurological disorders or trauma could be prevented from permanent paralysis by the introduction of stem cells, triggered to differentiate into neural cells. An area that particularly sticks out as potentially benefiting from stem cell technology is that of recovering lost skin. Vets so often have to take skin from other parts of an animal s body, and perform painstaking skin grafts, sometimes with little success, in order to repair damage done by any number of factors, from parasitic destruction to burns. In fact one of the most common cases for a small animal vet is that of the Road Traffic Accident. RTAs are brought in regularly, with skin ripped and torn in numerous parts of the body. In the cases of small wounds, this is a less major concern, since they can easily be sutured. However, in extreme cases, the patient may have large areas of raw flesh, which simultaneously need to heal, whilst the body s healing mechanisms are also attempting to deal with broken ribs or a fractured pelvis. Instead of removing skin from another area, a new piece of skin could be cultured in a lab, then stitched on. If the stem cells had come from a different individual, the problem of rejection might occur. However, it is entirely credible that if the technology was developed, breeders of show animals might well take care to ensure that new arrivals in the pedigree were insured against future accident by harvesting Wharton s jelly and /or 4

5 cord blood at birth. This could be utilised in a variety of circumstances. The potential of stem cell technology to improve the veterinary treatment of cancer is vast. Current treatment such as radiotherapy and chemotherapy are extremely unpleasant for the animal, not to mention dangerous for the practitioner to administer. However, stem cells could be used to improve the situation in one of two ways. Firstly, there is current research into the possibility that if stem cells were manipulated in the right way, they might be able to attack cancerous cells themselves. However, since cancer cells are considered self by the immune system, it would be necessary for the stem cells to be adapted to recognise cancerous cells and so attack them but no surrounding self cells. In the meantime, I would like to discuss how stem cells could be used to alleviate side effects of current cancer treatment: Chemotherapy involves the use of chemicals which affect cells undergoing rapid cell division. Since cancer cells divide much more frequently than healthy cells, they are the prime targets. However, there is the risk that chemotherapy can destroy healthy cells which happen to be dividing, since the chemicals do not differentiate between cancer and non-cancer and this may cause problems in areas of the body where growth or regeneration occurs frequently. These are the parts of the body most likely to be affected by the side effects of chemotherapy. The notorious loss of hair which sometimes accompanies treatment in humans results from the fact that growth continually occurs in the hair follicles. The skin is also continuously growing as the dead outer layer falls away, and in the digestive tract the endothelium is replaced as acid, enzymes and food wear cells away, so these areas are also commonly affected by use of chemotherapy in humans. Fortunately, due to lower doses of drugs and less mixing, most companion animals (around 95%) do not suffer severe side-effects from chemotherapy. The most common problems are to do with the digestive system; irregular and infrequent bouts of diarrhoea and/or vomiting may result in hospitalisation of the animal for a few days, as may infections which arise as a result of the drugs effect on white blood cell production in the bone 5

6 marrow. These are in fact usually caused by bacteria already living in the animal, so that hygiene alone cannot prevent these opportunistic infections. Hair loss is rare in cats and dogs, although each patient is different, as are the different drugs. Although side effects are so limited, and drugs are prescribed to control those that are likely to occur, stem cells provide a potential solution. Adult stem cells are already used to give immuno-deficient humans bone marrow transplants, so perhaps multipotent cells could be used to boost the immune system so that chemotherapy would leave it not so depleted, thus preventing the albeit brief) period of subsequent vulnerability. Similarly, the lining of the gut could be given a helping hand, to prevent the effects of temporary damage during therapy. Adult stem cells found in hair follicles are already hoped to be able to regenerate hair growth. Veterinary medicine can rarely, at present, offer complete recovery from cancer for animals, rather using low dosage treatments to trigger remission. During remission, quality of life for the animal can remain quite good and its life expectancy is increased by treatment. However, many owners and vets feel that it is not in a certain animal s best interests to prolong its life only briefly with treatment that will be potentially traumatic. However, if the negative effects of chemotherapy could be reduced from small to negligible, then perhaps it would become the most viable option for more owners, and pets would be able to live longer, happier lives, in spite of cancer. If side effects could be rendered negligible, doses could potentially also be increased, leading to a higher rate of total remission. However this option is perhaps not ideal, since higher dosage would be very expensive, not to mention dangerous for owners and veterinary staff. 6

7 CONCLUSION Stem cell technology has the potential to transform veterinary medicine, by providing ways to stimulate the body s regeneration. Advances could be made in the fields of inherited diseases, aging, accidents and cancer. In particular, stem cells might prove useful in treating animals that have lost skin, or by reducing the negative effects of pre-existing treatments, such as chemotherapy. Despite the controversy surrounding embryonic stem cell research, I propose that there is a way forward with the use of Wharton s jelly, obtained from the umbilical cord after birth. This may prove particularly effective in animal species where multiple births are normal, due to the amount of material available. However, some problems still remain. A great deal is still unknown about the triggers needed for a stem cell to differentiate into a particular, chosen type of specialised cell. Since the technology is so knew there is little evidence as to the likely success of the proposed applications in animal medicine. In addition, the likely cost of such future treatments may mean that it is the destined for use restoring champion race horses or in treating hereditary disease or fertility in endangered species in our zoos. 7

8 REFERENCES Mesenchymal Stem Cells in the Wharton s Jelly of the Human Umbilical Cord Matrix cells from Wharton's jelly form neurons and glia. Report from Department of Anatomy and Physiology, Kansas State University, Manhattan, Kansas Wharton's Jelly, Hair Follicles New Sources of Adult Stem Cells, Studies Find Transplant News 13 May Report into Stem Cell Research at Kansas State University 8