- Prof. Anthony J.F. d’Apice, Principal Investigator
- Dr. Peter J. Cowan, Co-Investigator
- Dr. Trixie A. Shinkel, Associate
- St. Vincent’s Hospital Melbourne, Australia
- Prevention of rejection of organ transplants between species by anti-oxidant genes
Transplantation of organs between different species (e.g. pig to human) is a possible solution to the chronic shortage of human organs for transplantation. However, this is currently not possible because the human immune system recognizes the pig organ as foreign and mounts a rapid and vigorous rejection response. This rejection response can be divided into two stages: hyperacute rejection and acute vascular rejection. The first stage occurs within minutes to hours by binding of human antibodies to the surface of the pig organ and subsequent activation of the human immune system. It is now generally accepted that this process can be overcome by genetic modification of the donor organ. The next phase of rejection occurs over a period of days to weeks and is a complex process involving multiple factors. One damaging factor believed to be involved in this process is oxidative stress. Under normal conditions, a balance between oxidants and antioxidant mechanisms is maintained due to the presence of antioxidant enzymes such as superoxide dismutase, catalase and glutathione peroxidase. If this balance is disrupted to favour the overproduction of oxidants, as occurs during transplantation of organs, the antioxidant enzymes will no longer be able to cope with the removal of excess oxidants and thus loss of the donor organ will occur. The hypothesis of this study is that increasing the expression of antioxidant enzymes in the donor animal using current genetic technology will protect the organ from injury caused by oxidants and thus prolong survival. Initial studies will be carried out to determine the best combination of antioxidant enzymes to be used for the subsequent generation of experimental animals. Animals expressing this combination of antioxidant enzymes will be examined to determine whether their organs are protected from transplantation-associated injury.