- Prof. Mauro Sandrin, Principal Investigator
- Austin Research Institute, Heidelberg, Australia
- Reduction of Galalpha(1,3) Gal for Xenotransplantation: Studies of HAR/DXR
Advances in surgical and immunosuppressive techniques have led to organ transplantation as the method of choice for the treatment of many diseases. However, the number of suitable donors is dwindling, due to many factors, but largely as a result of the reduction in deaths from car accidents. Xenotransplantation, the transplantation of organs from species other than humans, is now seen as a viable solution to the world-wide problem of lack of supply of suitable human donors. The pig is the most suitable for a variety of reasons. However, the problem is that all humans contain natural antibodies to the pig, which would lead to rejection within a few minutes because the antibodies bind to the transplant and induce its rapid destruction (so called "hyperacute rejection"). Recent studies from our laboratory have indicated that most, if not all, of the antibodies react with the sugar galactose, which is on many molecules on the surface of transplanted pig tissues. Our studies have indicated very large amounts of this material in pig blood vessels - guaranteeing the early rejection of transplanted organs such as kidney, heart and liver. The production of pigs that do not express galactose is an important pre-requisite for successful xenotransplantation. While mice that lack this sugar have been produced, and indeed form the basis of our models, the technology to perform this in pigs is not available. We have recently described an alternative strategy to reduce the amount of galactose expressed by transgenic animals, a technique that is suitable for the production of transgenic pigs. We will examine a number of different transgenic mice expressing a combination of genes that reduce the expression of galactose and determine the effects of these modifications on organ and cell transplantation. These studies will be the prelude to the production of pigs that could be used for human transplantation.