Determining The Potential For Porcine Foetal Islet Xenotransplantation.
Funder
National Health and Medical Research Council
Funding Amount
$351,660.00
Summary
Tight glucose control by insulin injection minimises diabetic complications but restricts lifestyle. An alternative, pancreatic islet transplantation, is limited by donor shortage. With genetic technology, pig donor tissue is a feasible donor source. This project will use an inbred pig colony to assess long term foetal pig islet function in the absence of an immune response. It will outline the genetic characteristics of this pig colony and carefully catalogue the type, number and distribution o ....Tight glucose control by insulin injection minimises diabetic complications but restricts lifestyle. An alternative, pancreatic islet transplantation, is limited by donor shortage. With genetic technology, pig donor tissue is a feasible donor source. This project will use an inbred pig colony to assess long term foetal pig islet function in the absence of an immune response. It will outline the genetic characteristics of this pig colony and carefully catalogue the type, number and distribution of endogenous retroviruses within pig genes. It may provide a basis from which new strategies can be developed to overcome rejection. Ultimately a unique Australian resource will be developed which may provide unlimited islets for safe, large-scale transplantation of diabetics before they develop debilitating complications.Read moreRead less
Major Xenoantigens For Neovascularised Porcine Xenografts: The Role Of PERV And MHC In Rejection And Tolerance
Funder
National Health and Medical Research Council
Funding Amount
$504,750.00
Summary
Cross-species transplants (xenografts) of pig organs which use donor pig blood vessels are rejected by antibody which recognises a special target (xenoantigen) on the pig blood vessels; other pig tissue transplants (cellular transplants) which use recipient (not donor pig) blood vessels, are rejected by white blood cells called CD4 T cells. The pig targets recognised by the xenoreactive CD4 T cells are unknown. We plan to identify the major target(s) involved in cellular xenograft rejection. Thi ....Cross-species transplants (xenografts) of pig organs which use donor pig blood vessels are rejected by antibody which recognises a special target (xenoantigen) on the pig blood vessels; other pig tissue transplants (cellular transplants) which use recipient (not donor pig) blood vessels, are rejected by white blood cells called CD4 T cells. The pig targets recognised by the xenoreactive CD4 T cells are unknown. We plan to identify the major target(s) involved in cellular xenograft rejection. This information can then be used to specifically remove or disable only those CD4 T cells capable of recognising the pig tissue and hence facilitate xenograft survival or tolerance without immunosuppression. In this way, the remainder of the CD4 T cell population and immune system is preserved intact. Recent studies have demonstrated that a pig virus (PERV) can be transmitted from pig tissue xenografts to recipient tissues. Our studies have also suggested that the process of xenograft rejection and the immunological recognition of transplant recipient cells infected with the pig virus, are closely related. We plan to investigate this relationship and ascertain whether the immunological destruction of the pig tissue xenograft is largely due to an immune response generated against the pig virus(es) it carries. As an extension of this concept, we will investigate whether long-term xenograft survival (tolerance) is associated with lack of immune reactivity to the pig virus and hence a continual capacity for pig virus to be transmitted to host tissues. This outcome could result in the development of unwanted disease(s) in transplant patients. To prevent these problems, our studies will determine whether it will be essential for such pig virus to be eliminated from the donor pig tissue before transplantation, e.g. by the development of potent anti-viral agents and-or via the development of pig herds that have been genetically engineered to be pig virus (PERV)-deficient.Read moreRead less