The immense potential of xenotransplantation in surgery.
There is a limited availability of deceased human organs and cells for the purposes of clinical transplantation. Genetically-engineered pigs may provide an alternative source. Although several immune barriers need to be overcome, considerable progress has been made in experimental models in recent years, largely through the increasing availability of pigs with new genetic modifications. Pig heterotopic heart graft survival in nonhuman primates has extended for 8 months, with orthotopic grafts supporting life for almost 2 months. Life-supporting kidney transplants have functioned for almost 3 months. The current barriers are related to coagulation dysfunction between pig and primate that results in thrombotic microangiopathy and/or a consumptive coagulopathy, which may in part be related to molecular incompatibilities in the coagulation systems of pigs and primates. Current efforts are concentrated on genetically-modifying the organ- or islet-source pigs by the introduction of 'anticoagulant' or 'anti-thrombotic' genes to provide protection from the recipient coagulation cascade and platelet activation. Progress with pig islet xenotransplantation has been particularly encouraging with complete control of glycemia in diabetic monkeys extending in one case for >12 months. Other areas where experimental data suggest the possibility of early clinical trials are corneal xenotransplantation and pig neuronal cell xenotransplantation, for example, in patients with Parkinson's disease. With the speed of advances in genetic engineering increasing steadily, it is almost certain that the remaining problems will be overcome within the foreseeable future, and clinical allotransplantation will eventually become of historical interest only.
Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, BST W1543, 200 Lothrop Street, Pittsburgh, PA 15261, USA. cooperdk@upmc.edu
David K C
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D000818:Animals; D030801:Animals, Genetically Modified; D017690:Cell Transplantation / Q000379:methods*; D016039:Corneal Transplantation / Q000379:methods; D017707:Erythrocyte Transfusion / Q000379:methods; D005818:Genetic Engineering; D006801:Humans; D016381:Islets of Langerhans Transplantation; D009474:Neurons / Q000637:transplantation; D016377:Organ Transplantation / Q000379:methods*; D011323:Primates; D013552:Swine / Q000235:genetics; D014183:Transplantation, Heterologous / Q000009:adverse effects / Q000276:immunology / Q000502:physiology