Xenotransplantation - Nuffield Council on Bioethics

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Animal-to-Human Transplants : the ethics of xenotransplantation 2.21 Infection is a major problem with artificial lungs, since they are in constant contact with the atmosphere and do not have the natural protection mechanisms found in human lungs. Blood clotting is another problem that must be overcome before artificial lung implants become a realistic option. Bioengineered organ and tissue replacements 2.22 As indicated above, reproducing the complicated functions of the body in a purely mechanical way is extremely difficult. This has led to the development of artificial organs incorporating living cells, tissues or organs which can perform some of the functions of the tissue or organ that needs replacing. Liver 2.23 The liver performs a wide range of important functions including the processing of the products of digestion, the control of the metabolism of proteins and carbohydrates, the manufacture of essential proteins such as blood clotting factors, the removal of toxic substances absorbed from the gut, the excretion of the breakdown products of red blood cells and the secretion of bile. It is impossible at present to begin to replicate all of these complicated functions by wholly artificial means, so research has focused instead upon bioengineered livers. The intention is to use them on a short-term basis to keep patients suffering from liver failure alive while they wait for a transplant or to give their own liver a chance to regenerate. At the simplest level, the patient’s blood is passed through an animal liver: at best this can keep patients alive for a very short time. 23 2.24 Implantable artificial livers are a long way off, but clinical trials are under way for artificial livers which function outside the body. One such device is the extracorporeal liver assist device, which has been used successfully in small numbers of patients. 24 The device filters blood through thousands of tiny porous tubes. Human liver cells are packed around the tubes to process the passing blood and to get rid of waste. The liver cells are immortalised (they have the ability to keep reproducing) and can be grown in the laboratory. It is important that the liver cells do not enter the blood, as there is a chance that if they passed into the body and became established in an organ or tissue, they might develop into tumours. 23 Chari R et al. (1994) Brief report: Treatment of hepatic failure with ex vivo pig-liver perfusion followed by liver transplantation. New England Journal of Medicine, 331:234-7. 24 McNair A N B et al. (1995) Recent advances : hepatology. British Medical Journal, 311:1351-5. 20
Alternatives to xenotransplantation 2.25 Other devices contain pig liver cells. The person’s blood is separated before treatment, with the cells being removed and only plasma entering the device. Eliminating the cells reduces the risk of blood clot formation, but the lack of red blood cells means that the liver cells in the machine suffer from a lack of oxygen. Alternative methods of supplying the liver cells with oxygen have been tried, but so far the cells have died within eight hours or so. 2.26 A different approach is to try and produce a true replacement liver grown in the laboratory. 25 An artificial scaffolding rather like a sponge is produced, made either from biodegradable or from tough and inert material. Blood vessels and liver cells are encouraged to grow onto the scaffolding. If successful, organs made in this way could then be used for transplantation. All these methods of liver replacement, however, are far from becoming routine clinical procedures. Pancreatic islet cells 2.27 Like the liver, the pancreas performs complicated biochemical functions which are difficult to replicate by artificial means. Efforts have been made to improve the success of transplantation of living islets of Langerhans, the pancreatic cells that produce insulin. 26 This would be used to treat patients suffering from diabetes. The islet cells are encapsulated in a porous membrane that does not cause an immune response. Blood passes through the membrane, and the trapped pancreatic cells produce insulin and help regulate the level of blood sugar. Since the islet cells remain separate from the blood, and from the cells of the recipient’s immune system, there is no immune response to the transplant. This suggests that the pancreatic cells could be supplied by non-compatible human donors or by other animals. Bones and joints 2.28 Techniques for repairing bones and joints using artificial materials are well established, and have become more successful with improvements in the materials used. These must be tough, lightweight, corrosion resistant and they must not cause an immune response. Stainless steel, used in hip replacements, and bone cements, however, shield the surrounding bone from stress and lead to wasting of the natural material. Thus, there is considerable interest in developing bioengineered bone in 25 Miller S K (1992) Cells and sponge support failing liver. New Scientist, 1 August 1992, p 20. 26 Soon-Shiong P et al. (1994) Insulin independence in a type 1 diabetic patient after encapsulated islet transplantation. Lancet, 343:950-1. 21
Page 1 and 2: NUFFIELD COUNCIL ON BIOETHICS Anima
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Page 6 and 7: Preface Preface Since the N
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Page 10 and 11: Working Party on Xenografts Working
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Conclusions and recommendations
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Animal-to-Human Transplants : the e
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Xenotransplantation - Nuffield Council on Bioethics

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