Complement Regulation: Protection Against Xenograft Rejection, Ischaemia and Reperfusion Injury [ 2002 - 2004 ]

Research Grant

Researchers: A/Pr Bruce Loveland (Principal investigator) ,  Ian Mckenzie

Brief description Organ transplantation is an accepted solution to treat kidney, heart, lung and liver failure, and is being keenly sought for diabetes treatment. With refined surgical techniques and better controlled immunosuppression, the expected graft survival times are in years. However, the number of individuals who would benefit from transplants exceeds the supply of donor organs, and this number will increase as the benefits of having a transplanted organ increase. There is an active program to research the possibility of using animal organs (xenografts). This project addresses one of the many issues arising from xenograft transplantation - the rapid activation of the body's complement system, which without treatment results in the very rapid rejection of the graft. In principle this problem can be solved by the development of transgenic donor animals that carry one or more human genes that produce a complement regulating protein, such as CD46 (MCP) or CD55 (DAF). In practice, however, to get successful longterm organ function still requires the selection of the optimal complement regulator or combination of regulators and an understanding of how they function. This research work analyses how CD46 and CD55 function to protect tissues from complement activation, and will result in selection of appropriate transgenes for xenografting. Another aspect of transplantation that is addressed in this proposal is the damage that a graft suffers when the blood supply is temporarily removed during organ harvest and the grafting procedure. This is similar to what occurs during a heart attack when a portion of heart muscle is starved of blood: as the blood flows again through the tissue there is a powerful reaction, again involving complement activation, which is known as reperfusion injury. We have found that perfusing a graft with a soluble form of the CD46 complement regulator provides protection against this damage. The research will measure and optimise this protection.

Funding Amount $AUD 256,980.00

Funding Scheme NHMRC Project Grants

Notes Standard Project Grant