Activin A And Follistatin Are Potential Key Regulators Of Organ Transplant Dysfunction And Graft Survival.
Funder
National Health and Medical Research Council
Funding Amount
$535,579.00
Summary
The grant examines novel key regulators in organ transplantation. It examines molecules that are released during transplant surgery and on the return of blood flow to the organ which can cause inflammation and scarring. The release is increased by heparin, an anticoagulant used in organ preparation. Alternative anticoagulants and blockers of the regulators released will be tested to prevent the damage to the transplant, potentially improving both the short and long term graft survival and functi ....The grant examines novel key regulators in organ transplantation. It examines molecules that are released during transplant surgery and on the return of blood flow to the organ which can cause inflammation and scarring. The release is increased by heparin, an anticoagulant used in organ preparation. Alternative anticoagulants and blockers of the regulators released will be tested to prevent the damage to the transplant, potentially improving both the short and long term graft survival and function.Read moreRead less
Enkephalin Metabolism In Cardiac Ischemia, Heart Failure And Cardiac Surgery
Funder
National Health and Medical Research Council
Funding Amount
$327,037.00
Summary
It has recently been discovered in animal studies that heart muscle can make its own opioid proteins. Previously, it was thought that only nerves made and released opioids. We have recently found that a class of opioids called enkephalins are made and then depleted from the heart during the stress of oxygen and nutrient deprivation. Enkephalins have been found to have potent metabolic effects on the heart. Previous work has shown that opioids can protect the heart against injury incurred during ....It has recently been discovered in animal studies that heart muscle can make its own opioid proteins. Previously, it was thought that only nerves made and released opioids. We have recently found that a class of opioids called enkephalins are made and then depleted from the heart during the stress of oxygen and nutrient deprivation. Enkephalins have been found to have potent metabolic effects on the heart. Previous work has shown that opioids can protect the heart against injury incurred during disease that restricts energy and oxygen supply to the blood vessels and heart. We wish to demonstrate this for the first time in human heart, and we will explore whether the production of enkephalins is altered by the stresses of cardiac surgery and heart failure. Understanding how the human heart attempts to protect itself in disease and how enkephalins work under these conditions, may prove valuable in the development of new drug therapy with synthetic drugs which mimic the action of enkephalins for heart protection during cardiac surgery, heart transplantation and ischemic heart disease. We will test whether specific enkephalins may be used to improve donor heart viability for transplantation by improving the duration and quality of preservation during storage. Understanding what happens to enkephalin production and metabolism in the failing hearts of patients may allow us to find new therapeutic targets in heart failure.Read moreRead less
Unraveling Mechanisms Of Liver Transplant Tolerance
Funder
National Health and Medical Research Council
Funding Amount
$694,822.00
Summary
Liver transplants are unique amongst solid organs as they are spontaneously accepted across different individuals and induce acceptance of other organs from the same donor co-transplanted at the same time. Using a new mouse liver transplantation model, this proposal will elucidate how the liver tissue performs this function and identify new markers associated with tolerance in the blood of mice. This knowledge will be used to identify liver transplant patients with reduced rejection risk.
NON IMMUNOLOGICAL BARRIERS TO SUCCESSFUL TREATMENT OF DIABETES BY XENOTRANSPLANTATION
Funder
National Health and Medical Research Council
Funding Amount
$310,500.00
Summary
Tragically patients whom suffer from diabetes mellitus develop major secondary complications such as renal failure, even with today's tight glucose control. Insulin injections minimise diabetic complications but restricts lifestyle and an alternative, pancreatic islet cell 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 pig fetal and neonatal islet cell function in ....Tragically patients whom suffer from diabetes mellitus develop major secondary complications such as renal failure, even with today's tight glucose control. Insulin injections minimise diabetic complications but restricts lifestyle and an alternative, pancreatic islet cell 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 pig fetal and neonatal islet cell function in combination with a kidney graft in the absence of an immune response. Using this specifically inbred pig colony we will carefully catalogue the type, number and distribution of endogenous retroviruses within pig genes. Using new and novel techniques we will develop a new strategy by which we can block and overcome this major concern of xenotransplantation. Ultimately a unique Australian resource will be developed which may provide unlimited islets for safe, large-scale transplantation of diabetics before they develop debilitating secondary complications from their diabetes and provide an alternative to the only current method of curing endstage renal failure with a combined pancreas and kidney transplant.Read moreRead less
Improved Ex-vivo Culture Of Keratinocytes For Clinical Applications
Funder
National Health and Medical Research Council
Funding Amount
$275,203.00
Summary
Skin cells grown for clinical applications currently require animal-derived cells and-or non-defined products for their expansion in the laboratory; these reagents can potentially infect patients who receive these therapies. This project will identify the essential components provided by these reagents and develop a fully synthetic and defined culture system. This improvement will provide safer, cost-effective grafts and cell-based therapies that will benefit patients suffering burns and wounds.