Elucidating Sub-clinical Pathways To Chronic Rejection In Lung Transplantation And Therapeutic Implications
Funder
National Health and Medical Research Council
Funding Amount
$416,587.00
Summary
Organ transplantation has become a feasible option for many end-stage clinical conditions, including advanced lung disease. However, despite often dramatic short term successful outcomes, late graft dysfunction due to chronic rejection remains a major obstacle to long-term success. This is particularly the case in lung transplantation despite the use of potent broad spectrum immunosuppressive agents. The three major risk factors that have been identified for chronic rejection following lung tran ....Organ transplantation has become a feasible option for many end-stage clinical conditions, including advanced lung disease. However, despite often dramatic short term successful outcomes, late graft dysfunction due to chronic rejection remains a major obstacle to long-term success. This is particularly the case in lung transplantation despite the use of potent broad spectrum immunosuppressive agents. The three major risk factors that have been identified for chronic rejection following lung transplantation are acute rejection episodes diagnosed on lung biopsy, reactivation of the ubiquitous human DNA virus CMV and persistent lymphocytosis in the transplanted lung suggesting that potent broad spectrum immunosuppression may have both beneficial and harmful effects in lung transplant recipients. This proposal will apply sensitive new immunological techniques to detect and quantitate each of these risk factors at a sub-clinical level with a view to delineating their relationship with each other and with the development of chronic rejection following lung transplantation. This information will help unravel the pathogenesis of chronic rejection in lung transplant recipients and improve clinical management decisions in these patients and therefore long term health outcomes.Read moreRead less
Targeting Innate Immunity To Prevent Chronic Dysfunction Of The Transplanted Kidney
Funder
National Health and Medical Research Council
Funding Amount
$497,057.00
Summary
Kidney transplantation is the optimal treatment for patients suffering from end-stage kidney disease. Chronic transplant dysfunction is the major barrier to long-term health after transplantation, and is the subject of this application. Our studies suggest a signaling system activates immunity and leads to chronic transplant dysfunction. We aim to block this signaling system in mouse models to identify clinically applicable treatments to prevent kidney transplant failure.
A Preclinical Model Of Pig Islet Xenotransplantation As Treatment For Type 1 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$4,380,000.00
Summary
The object of this multi-disciplinary program grant is to develop a source of pig insulin secreting tissue that will be used to treat type 1 diabetic patients. At present the number of diabetic patients that would benefit from islet transplantation far outnumber any human source of this tissue. Pigs that have been genetically altered to avoid rejection and enhance survival could overcome this donor shortage problem.. It is our belief that with the appropriate genetic modification pig insulin-sec ....The object of this multi-disciplinary program grant is to develop a source of pig insulin secreting tissue that will be used to treat type 1 diabetic patients. At present the number of diabetic patients that would benefit from islet transplantation far outnumber any human source of this tissue. Pigs that have been genetically altered to avoid rejection and enhance survival could overcome this donor shortage problem.. It is our belief that with the appropriate genetic modification pig insulin-secreting tissue can avoid the aggressive rejection response that occurs with xenographs and provide normal blood glucose control without insulin. This project concentrates on the five main issues that need to be overcome before pig insulin-secreting tissue can be used in diabetics. These are: identifying the best source of insulin secreting tissue to use; adult islets, newborn or foetal islet cell clusters; overcoming the strong rejection response to pig tissue; identifying a safe and effective immunosuppressive regime; producing a new types of genetically modified pigs that will provide islets tissue that will work in humans; and demonstrating that pig islet transplantation will not pose undue infective risks for the patient or community. This truly collaborative program grant has brought together a large group of investigators with strong research records in diabetes, islet transplantation, xenotransplantation, pig transgenesis and pig genetics and includes scientists and clinicians who look after diabetic patients. Unique pig resources will be used including genetically manipulated pigs that have been shown to avoid some of the rejection mechanisms associated with transplanting pig tissue. There is a captive-bred baboon colony that provided a unique model of diabetes. A world class pig transgenesis facility has been enlisted to generate new lines of genetically altered pigs as new data is produced within the group. Finally because of the involvement of the National Pancreas Transplant Unit any proven therapeutic strategy can be brought quickly to clinical trials.Read moreRead less