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Round Table
1st FEMS Congress / Round Table 27^27
RT1^1 XENOTRANSPLANTATION: THE RISK OF RETROVIRUS INFECTION R. A. Weiss Dept. of Immunology and Molecular Pathology, University College London, U.K. Xenotransplantation is the grafting of animal cells, tissues and organs to humans. Although killed tissues such as bovine and porcine heart valves have been successfully transplanted in the clinic for many years, it is only recently that animal cells have been transferred for conditions such as Parkinson’s disease, type I diabetes or fulminant liver failure. Pigs are the favoured source of animal tissues and organs because they can be reared in speci¢c pathogen free conditions and are amenable to genetic modi¢cation by transgene and knock-out technology. However, there is a danger that animal pathogens may transfer to humans and infect not only the xenograft recipient but also his or her contacts and onwards to the community at large. Porcine endogenous retroviruses (PERV) are a particular concern because they cannot be eliminated from speci¢c pathogenfree pigs. PERV are linked to lymphoma in pigs, though a causal relationship has not yet been established. Two of three infectious strains of PERV can infect human cells in culture, but there is no evidence to date that humans exposed to live porcine tissues have become infected by PERV. The properties of PERV and their interactions with human cells will be described. RT1^2 THE CASE FOR XENOTRANSPLANTATION
transplantation for obliterative bronchiolitis following bone marrow transplantation. Prophylactic liver transplantation is now being undertaken for patients with inborne errors of metabolism to prevent neurological sequelae, and transplantation of ‘non-failing’ hearts is now considered for patients with hypertrophic occuclisive cardiomyopathy and muscular dystrophy. Although many grafts have survived for more than 20 years, there is a steady attrition caused by chronic rejection and graft vasculopathy. Transplant units then have to decide whether the recipient should be re-grafted, bearing in mind that graft and patient survival is signi¢cantly worse following retransplantation. With increasing numbers of children being transplanted, the pressure to re-transplant is enormous. The number of solid organ transplants performed is limited by the availability of donors. Attempts have been made to increase this donor pool, either by legislating for implied consent, public information campaigns, organ splitting and optimising graft preservation. Donor-related transplantation is an option in kidney, lung and liver recipients, but involves signi¢cant risk for the donor. The use of non-heart-beating donors has increased the donor pool slightly, but here retrieval of organs depends on a rapid response team and has signi¢cant resource implications. The number of patients waiting for transplants is increasing and the number of donor organs has levelled out and so demand is outstripping supply. To give waiting patients some realistic hope of a transplant, alternative strategies must be explored. Xenotransplantation has been tried in the past, but patients died within weeks because of uncontrollable graft rejection. The use of organs from transgenic animals with human antigens may go some way to minimise the incidence of rejection, and may buy time for patients until propagation of human organs ex-vivo or technological substitutes have obviated the need for cadaveric transplantation.
F. K. Gould Department of Microbiology, Freeman Hospital, Newcastle upon Tyne, NE7 7DN, UK Solid organ transplantation is now a well-recognised therapy for the management of a number of end-stage conditions. The indications for transplantation are increasing steadily and now include many iatrogenic conditions, such as heart transplantation for anthracycline induced cardiomyopathy following chemotherapy for leukaemia and other malignancies, renal transplantation for solid organ recipients treated with calcineuron inhibitors and lung 0378-1097 6 2003 Published by Elsevier Science B.V. on behalf of the Federation of European Microbiological Societies.
FEMSLE Congress 2-6-03
RT1^1 XENOTRANSPLANTATION: THE RISK OF RETROVIRUS INFECTION R. A. Weiss Dept. of Immunology and Molecular Pathology, University College London, U.K. Xenotransplantation is the grafting of animal cells, tissues and organs to humans. Although killed tissues such as bovine and porcine heart valves have been successfully transplanted in the clinic for many years, it is only recently that animal cells have been transferred for conditions such as Parkinson’s disease, type I diabetes or fulminant liver failure. Pigs are the favoured source of animal tissues and organs because they can be reared in speci¢c pathogen free conditions and are amenable to genetic modi¢cation by transgene and knock-out technology. However, there is a danger that animal pathogens may transfer to humans and infect not only the xenograft recipient but also his or her contacts and onwards to the community at large. Porcine endogenous retroviruses (PERV) are a particular concern because they cannot be eliminated from speci¢c pathogenfree pigs. PERV are linked to lymphoma in pigs, though a causal relationship has not yet been established. Two of three infectious strains of PERV can infect human cells in culture, but there is no evidence to date that humans exposed to live porcine tissues have become infected by PERV. The properties of PERV and their interactions with human cells will be described. RT1^2 THE CASE FOR XENOTRANSPLANTATION
transplantation for obliterative bronchiolitis following bone marrow transplantation. Prophylactic liver transplantation is now being undertaken for patients with inborne errors of metabolism to prevent neurological sequelae, and transplantation of ‘non-failing’ hearts is now considered for patients with hypertrophic occuclisive cardiomyopathy and muscular dystrophy. Although many grafts have survived for more than 20 years, there is a steady attrition caused by chronic rejection and graft vasculopathy. Transplant units then have to decide whether the recipient should be re-grafted, bearing in mind that graft and patient survival is signi¢cantly worse following retransplantation. With increasing numbers of children being transplanted, the pressure to re-transplant is enormous. The number of solid organ transplants performed is limited by the availability of donors. Attempts have been made to increase this donor pool, either by legislating for implied consent, public information campaigns, organ splitting and optimising graft preservation. Donor-related transplantation is an option in kidney, lung and liver recipients, but involves signi¢cant risk for the donor. The use of non-heart-beating donors has increased the donor pool slightly, but here retrieval of organs depends on a rapid response team and has signi¢cant resource implications. The number of patients waiting for transplants is increasing and the number of donor organs has levelled out and so demand is outstripping supply. To give waiting patients some realistic hope of a transplant, alternative strategies must be explored. Xenotransplantation has been tried in the past, but patients died within weeks because of uncontrollable graft rejection. The use of organs from transgenic animals with human antigens may go some way to minimise the incidence of rejection, and may buy time for patients until propagation of human organs ex-vivo or technological substitutes have obviated the need for cadaveric transplantation.
F. K. Gould Department of Microbiology, Freeman Hospital, Newcastle upon Tyne, NE7 7DN, UK Solid organ transplantation is now a well-recognised therapy for the management of a number of end-stage conditions. The indications for transplantation are increasing steadily and now include many iatrogenic conditions, such as heart transplantation for anthracycline induced cardiomyopathy following chemotherapy for leukaemia and other malignancies, renal transplantation for solid organ recipients treated with calcineuron inhibitors and lung 0378-1097 6 2003 Published by Elsevier Science B.V. on behalf of the Federation of European Microbiological Societies.
FEMSLE Congress 2-6-03