Bridging The Gap In Kidney Transplantation Using Pigs As Donors
Funder
National Health and Medical Research Council
Funding Amount
$1,452,341.00
Summary
Chronic kidney failure results in patients suffering significant morbidity and mortality ultimately requiring life-supporting dialysis. Kidney transplantation and lifelong immunosuppression are the only treatment, but (i) is limited by the shortage of human donors and (ii) carries risks associated with these anti-rejection drugs. This project aims to solve both problems by using humanized pigs as donors combined with a novel approach to inducing acceptance of the transplanted kidneys.
Living kidney donation remains a complex ethical issue. The expectation is that the risks to the donor are outweighed by the benefits to the donor and recipient. The long-term risks to the donor are however uncertain. This is an international prospective cohort study of 310 donors and 310 non-donors, including the recruitment of 85 donors and 85 non-donors in Australia. We will determine the long term risks on a kidney donor of a series of physical and psychological health outcomes.
Detection Of Cardiac Allograft Rejection By Peripheral Blood Gene Expression: A Novel Concept Of Personalized Approach To Transplantation.
Funder
National Health and Medical Research Council
Funding Amount
$292,705.00
Summary
Heart biopsy is required to detect rejection after heart transplantation. The cost of each biopsy is around $7,000 and at least 10 heart biopsies needed in the first post-transplant year alone. The biopsy is difficult for the patients and significant cost for the Australian healthcare system. Thus, it would be beneficial to identify rejection using a simple blood test. Such tool would help to reduce or eliminate the need for expensive heart biopsy and would reduce the cost by about 10 times.
Protecting The Endothelial Glycocalyx To Improve Transplant Rates And Outcomes
Funder
National Health and Medical Research Council
Funding Amount
$725,180.00
Summary
A tiny, previously overlooked, structure called the endothelial glycocalyx (EG) is now known to ‘waterproof’ blood vessels. This grant extends our exciting preliminary data in the field of lung transplantation, where we have shown that EG loss is the main cause of a poorly functioning organ, to develop new tests of lung and kidney function, as well as treatments to resuscitate marginal organs outside the body, so improving access to and the safety of transplantation.
Mechanisms Of Regulatory T Cell Induction By Soluble Immunomodulatory Molecules
Funder
National Health and Medical Research Council
Funding Amount
$729,414.00
Summary
The purpose of this work is to identify how a select population of cells (T regulatory cells) function to prevent or dampen down the sometimes-harmful effects of the immune system. Understanding how these cells function may have broad implications for general immune regulation.
TOLERANCE OR REJECTION – THE ROLE OF INNATE IMMUNITY IN DETERMINNG THE FATE OF A KIDNEY ALLOGRAFT
Funder
National Health and Medical Research Council
Funding Amount
$506,413.00
Summary
Transplantation is the optimal management for people with organ failure. Tolerance, to retain transplant function without immunosuppression, remains the key goal but is seldom achieved. We propose to block Toll-like receptor signalling to achieve kidney transplant tolerance in mice. If successful, we would translate this into clinical trials in human, seeking to achieve organ transplantation without the risks of cancer, infection and premature death that are currently faced by organ recipients.
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
Elucidating The Mechanism Of IL-2 Cytokine/antibody Mediated Transplantation Tolerance
Funder
National Health and Medical Research Council
Funding Amount
$624,429.00
Summary
Organ transplantation is a life-saving treatment for end-stage organ failure. However, patients must take immunosuppressive drugs to prevent rejection, a lifetime of which increases the risk of infection and cancer. An alternative to drugs is to manipulate the immune system from within. We discovered a way to boost the immune ‘regulators’ so that they stifle the graft-destroying response. We are optimising this approach with the aim of transplanting organs without long-term immunosuppression.
Mechanisms Of Islet Graft Rejection And Acceptance
Funder
National Health and Medical Research Council
Funding Amount
$602,501.00
Summary
Islet grafts offer diabetic patients the promise of a return to insulin-independence. In this project we will study how natural regulatory T cells suppress islet graft rejection in a mouse model. We will determine where regulatory T cells interact with graft-rejecting T cells, and define the mechanisms used to mediate their suppressive effects. Our findings will aid in developing new ways to induce long-term acceptance of islet grafts without immunosuppressive drugs.
Strategies To Achieve Kidney Transplant Tolerance In A Clinically-relevant Model
Funder
National Health and Medical Research Council
Funding Amount
$663,490.00
Summary
The acceptance of kidney transplants without immunosuppression (tolerance) would avoid the side effects of these powerful drugs and improve long-term graft survival. Donor brain death causes inflammation in transplanted kidneys which can block tolerance. In this project, we aim to determine whether expression of a naturally-occurring soluble anti-inflammatory molecule in the liver can prevent this inflammation, allowing tolerance to develop.