Which Transgenic Pig Will Be Used For Islet Transplantation In Humans?
Funder
National Health and Medical Research Council
Funding Amount
$3,031,083.00
Summary
We propose that xenotransplantation of pig islets will cure Type 1 diabetes. This program will generate genetically modified pigs to overcome the molecular differences between pigs and humans by removing a pig gene and inserting several human genes. In addition, we will add immunosuppressive genes and so minimise the need for drug treatment of the diabetic recipient. We will test our hypothesis by transplanting islets from these genetically modified pigs into baboons. We suggest that this will p ....We propose that xenotransplantation of pig islets will cure Type 1 diabetes. This program will generate genetically modified pigs to overcome the molecular differences between pigs and humans by removing a pig gene and inserting several human genes. In addition, we will add immunosuppressive genes and so minimise the need for drug treatment of the diabetic recipient. We will test our hypothesis by transplanting islets from these genetically modified pigs into baboons. We suggest that this will provide an inexhaustible supply of islets for transplantation.Read moreRead less
Elimination of the transplant waiting list is the ultimate goal of research into pigto-human xenotransplantation. The prospect of success has been improved recently by refinements in technology used to introduce genetic modifications in the pig, although the genes that will need to be expressed or deleted are still undecided. What is clear is that intravascular thrombosis, a critical mediator of rejection of pig xenografts, must be overcome. This project aims to investigate the use of anticoagul ....Elimination of the transplant waiting list is the ultimate goal of research into pigto-human xenotransplantation. The prospect of success has been improved recently by refinements in technology used to introduce genetic modifications in the pig, although the genes that will need to be expressed or deleted are still undecided. What is clear is that intravascular thrombosis, a critical mediator of rejection of pig xenografts, must be overcome. This project aims to investigate the use of anticoagulant gene expression to prevent intravascular thrombosis associated with xenograft rejection.Read moreRead less
At least 6 young Australians are diagnosed each day with type 1 diabetes. This Program aims to change the way type 1 diabetes is managed by proactively treating its underlying mechanisms. We will develop safer and more effective immune therapies, develop islet transplantation, look for better markers of disease, and identify ways to preserve insulin-producing cells. The Program aims to propel type 1 diabetes research forward to reach the goals of prevention and cure.
Developing Clinical Islet Transplantation For Type 1 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$387,337.00
Summary
This fellowship will provide me the opportunity to advance islet transplantation as a curative treatment for people with type 1 diabetes. The ultimate goal is to use cell-based therapy to achieve insulin independence for all people with type 1 diabetes. It aims to do this by developing a collaborative network between scientists and clinicians to advance human islet transplantation as a treatment for type 1 diabetes and to develop genetically engineered pig cells as a novel source of insulin prod ....This fellowship will provide me the opportunity to advance islet transplantation as a curative treatment for people with type 1 diabetes. The ultimate goal is to use cell-based therapy to achieve insulin independence for all people with type 1 diabetes. It aims to do this by developing a collaborative network between scientists and clinicians to advance human islet transplantation as a treatment for type 1 diabetes and to develop genetically engineered pig cells as a novel source of insulin producing cellsRead moreRead less
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