The successful treatment of many conditions in which the relevant organ has failed completely and irreversibly is to replace the organ with a new one i.e. to perform a transplant. It is well known that there are far fewer organs available for transplantation than the number needed. This means that for those conditions where a supportive treatment is available, eg. the artificial kidney, patients must be maintained by that method, however for other organs such as hearts, lungs and livers, there i ....The successful treatment of many conditions in which the relevant organ has failed completely and irreversibly is to replace the organ with a new one i.e. to perform a transplant. It is well known that there are far fewer organs available for transplantation than the number needed. This means that for those conditions where a supportive treatment is available, eg. the artificial kidney, patients must be maintained by that method, however for other organs such as hearts, lungs and livers, there is no mechanical substitute. If these patients do not receive a transplant, they die. A solution to this problem is to use organs from animals. This is called xenotransplantation. The pig is the most suitable donor, however despite the many similarities to humans which make pigs suitable, there are many differences which are still to be overcome before we can use pig xenotransplants clinically. These differences are at a very fine molecular level and prevent the normal integration of the pig organ into the human recipient. It is well established that the single most important difference which causes this rejection is a sugar molecule like a blood group which pigs have but humans do not. This is called Gal. This is also present in most animal species and we have completely removed it from a strain of mice by genetic modification. Unfortunately it has not been possible to make this change in pigs. However, the genetically modified mice give us a test model to determine precisely how much and by what mechanisms the Gal antigen is responsible for the rejection process.Read moreRead less
Intravascular Coagulopathy In Discordant Xenotransplantation
Funder
National Health and Medical Research Council
Funding Amount
$447,750.00
Summary
The successful treatment of many conditions in which the relevant organ has failed completely and irreversibly is to replace that organ with a new one ie. to perform a transplant. It is well known that there are far fewer organs available for transplantation than the number needed. This means that for those conditions where a supportive treatment is available, eg. the artificial kidney, patients must be maintained by that method, however for other organs such as hearts, lungs and livers, there i ....The successful treatment of many conditions in which the relevant organ has failed completely and irreversibly is to replace that organ with a new one ie. to perform a transplant. It is well known that there are far fewer organs available for transplantation than the number needed. This means that for those conditions where a supportive treatment is available, eg. the artificial kidney, patients must be maintained by that method, however for other organs such as hearts, lungs and livers, there is no mechanical substitute. If these patients do not receive a transplant, they die. A solution to this problem is to use organs from animals. This is called xenotransplantation. The pig is the most suitable donor, however despite many similarities to humans which make it suitable, there are many differences which are still to be overcome before clinical application is possible. These differences are at a very fine molecular level and prevent the normal integration of the organ into the new recipient. The result is that the new organ is rejected within minutes. This process is called hyperacute rejection and by research into its mechanism it was found to be due to just a few differences. We and others have genetically modified pigs so that they have the human components and this has completely prevented this form of rejection. However,we have found a second barrier which causes a rejection response after a few days. It is now known that a major component of the cause of this second barrier is a few differences in the clotting system. We propose to make further genetic modifications which we think will prevent this rejection. This project proposes to examine various genetic modifications and test their effect in small animal models before going on to make and test pigs in which human anti-clotting genes have been inserted. . If we are successful, the possibility of replacing failed human organs with animal organs will be a step closer.Read moreRead less
Intravascular Coagulopathy In Discordant Xenotransplantation
Funder
National Health and Medical Research Council
Funding Amount
$227,036.00
Summary
The successful treatment of many conditions in which the relevant organ has failed completely and irreversibly, is to replace that organ with a new one ie. to perform a transplant. It is well known that there are far fewer organs available for transplantation than the number needed. This means that for those conditions where a supportive treatment is available, eg. the artificial kidney, patients must be maintained by that method, however for other organs such as hearts, lungs and livers, there ....The successful treatment of many conditions in which the relevant organ has failed completely and irreversibly, is to replace that organ with a new one ie. to perform a transplant. It is well known that there are far fewer organs available for transplantation than the number needed. This means that for those conditions where a supportive treatment is available, eg. the artificial kidney, patients must be maintained by that method, however for other organs such as hearts, lungs and livers, there is no mechanical substitute. If these patients do not receive a transplant, they die. A solution to this problem is to use organs from animals. This is called xenotransplantation. The pig is the most suitable donor, however despite many similarities to humans which make it suitable, there are many differences which are still to be overcome before we can use xenotransplants clinically. These differences are at a very fine molecular level and prevent the normal integration of the organ into the new recipient. The result is that the new organ is rejected within minutes. This process is called hyperacute rejection and by research into its mechanism it was found to be due to just a few differences. We and others have genetically modified pigs so that they have the human genes and this has completely prevented this form of rejection. However,we have found a second barrier which causes a rejection response after a few days. It is now known that a major component of the cause of this second barrier is a few differences in the clotting system. We propose to make further genetic modifications which we think will prevent this rejection. This project proposes to examine various genetic modifications and test their effect in small animal models before going on to make and test pigs into which human genes have been inserted. If we are successful, the possibility of replacing failed human organs with animal organs will be a step closer.Read moreRead less
Many people with organ failure need a transplant to survive. Unfortunately most patients who would benefit from a transplant are unable to receive one because of the shortage of living or deceased donors. A possible solution to this shortage is to use animal organs. Pigs are the most suitable animal donor. This project aims to produce and test genetically modified pigs which can provide organs that will be resistant to rejection when transplanted into human recipients.
The Role Of T-cell Apoptosis In Transplantation Tolerance
Funder
National Health and Medical Research Council
Funding Amount
$173,380.00
Summary
Organ transplantation is the treatment of choice for patients with end-stage heart, lung, liver or kidney failure and there have been spectacular improvements in the early success of these procedures. However the 10 year graft survival rate has not changed much in the past 15 years. One way of overcoming this problem is to manipulate the immune system so that the transplant is accepted indefinitely. This is called tolerance and it works by giving intense immunosuppression for a short period so t ....Organ transplantation is the treatment of choice for patients with end-stage heart, lung, liver or kidney failure and there have been spectacular improvements in the early success of these procedures. However the 10 year graft survival rate has not changed much in the past 15 years. One way of overcoming this problem is to manipulate the immune system so that the transplant is accepted indefinitely. This is called tolerance and it works by giving intense immunosuppression for a short period so that the transplant is accepted indefinitely without the need for long term immunosuppression. The immune mechanism responsible for this phenomenon is complex and is poorly understood. This project aims to study the early events in the immune system that leads to transplantation tolerance. In particular, factors involved in programmed cell death in white blood cells will be studied. Specially bred mice that have blocks in the cell death mechanisms will used to determine what effects these blocks have on the ability to induce tolerance. Other mice that have been genetically altered to allow their white cells to be tracked will be used to study the fate of these cells. If the mechanisms involved in tolerance induction are better understood, then it will be possible to design specific immunosuppressive drugs that will be used to produce tolerance in transplant patients.Read moreRead less