The Role Of Dendritic Cells In Graft-versus-host Disease After Allogeneic Stem Cell Transplantation.
Funder
National Health and Medical Research Council
Funding Amount
$317,633.00
Summary
Allogeneic bone marrow transplantation (BMT) remains the most effect curative treatment for patients with a number of malignant conditions, especially leukemia. Graft-versus-Host Disease (GVHD) ocurrs when the newly transplanted bone marrow (which includes the immune system) recognises the transplant recipient as foreign and mounts an immune attack against patient tissues. GVHD is the major complication of BMT and is responsible for the death of up to half of the patients who receive this proced ....Allogeneic bone marrow transplantation (BMT) remains the most effect curative treatment for patients with a number of malignant conditions, especially leukemia. Graft-versus-Host Disease (GVHD) ocurrs when the newly transplanted bone marrow (which includes the immune system) recognises the transplant recipient as foreign and mounts an immune attack against patient tissues. GVHD is the major complication of BMT and is responsible for the death of up to half of the patients who receive this procedure. Research to date by Dr Hill and colleages has provided substantial detail on how and why this process occurs. This information has led to a number of advances in the field which are already improving patient survival after BMT. This includes a new type of bone marrow transplantation that uses a naturally ocurring growth factor (called a cytokine) to allow the collection of immature bone marrow cells from the blood of transplant donors. The transplantation of these cells rather than bone marrow appears to reduce the chance of dying during BMT and also improves the cure rates from the underlying leukemia. In addition, Dr Hill has developed a novel method for preventing GVHD using different types of naturally ocurring growth factors called cytokine shields that help protect patient tissue from attack by the immune system. It has recently become clear that the immune system is directed by a subtype of white cells called dendritic cells and Professor Hart at the Mater Medical Research Institute has been a pioneer in this field. As initiators of the immune system it is likely that dendritic cells play a pivotal role in GVHD and Dr Hill and Prof Hart at the Mater Medical Research Institute will study DC within the context of Dr Hills newly developed therapies with the aim of further understanding the processes of GVHD. This work will allow manipulation of these cells during BMT in order to improve patient survival.Read moreRead less
Bone marrow transplantation (BMT) is the most effect treatment for a number of conditions, especially leukemia. Graft versus host disease (GVHD) is a complication of BMT and results in the death of up to 50% of transplant recipients. GVHD occurs when the newly transplanted immune system recognizes the recipient as foreign and mounts and immune reponse against the patients tissues. These studies will focus on identifying and understanding the function of the immune cells which drive GVHD.
Gene Transfer For Corneal Transplantation And Limbal Stem Cell Transplantation
Funder
National Health and Medical Research Council
Funding Amount
$743,463.00
Summary
The cornea is the clear window at the front of the eye. Corneal disease is the second most common reason for blindness in the world. It is sometimes made worse by additional disease affecting the ocular surface. Replacement of a damaged cornea, or of the elements that maintain a normal ocular surface, is possible by transplantation of tissue (either the cornea or the limbus) from a donor eye. The alternative, an artificial cornea, has never yet been reported to function nearly as well as does a ....The cornea is the clear window at the front of the eye. Corneal disease is the second most common reason for blindness in the world. It is sometimes made worse by additional disease affecting the ocular surface. Replacement of a damaged cornea, or of the elements that maintain a normal ocular surface, is possible by transplantation of tissue (either the cornea or the limbus) from a donor eye. The alternative, an artificial cornea, has never yet been reported to function nearly as well as does a successful corneal graft, because the interface between the patient and the prosthesis breaks down and serious problems such as infection are common. Transplantation of the cornea is very successful in some patients but in a sizable subgroup, the graft will fail because of an unwanted immune response. Rejection is the usual cause of a graft failure. Grafts to repair a damaged ocular surface also fail from rejection. Overcoming an unwanted immune response would improve the outcome of corneal transplantation by as much as thirty percent. Overcoming the twin problems of corneal graft rejection and ocular surface disease would make transplantation a feasible option for millions of blind individuals. Novel approaches to abrogation of the immune response to ocular tissue grafts are required, because the many developments in immunosuppression that have improved the survival of other types of transplants have not improved the outcome for grafts in the eye. The immunobiology of the eye is sufficiently different from that of solid organs to demand a different approach. We plan to investigate the use of localised gene transfer to donor eye tissue prior to transplantation, to improve corneal graft and limbal graft outcome.Read moreRead less