Blindness exerts major physical, emotional and economic constraints and hardship upon the sufferer. Transplant surgery can restore vision to many people who are visually impaired as a result of disease affecting the front of the eye. The transplant itself is taken from the eye of a person who has died, after consent from the donor's family. Our goal is to improve the outcome for patients who require transplants of tissue to the front of the eye, in order to restore their vision or to relieve pai ....Blindness exerts major physical, emotional and economic constraints and hardship upon the sufferer. Transplant surgery can restore vision to many people who are visually impaired as a result of disease affecting the front of the eye. The transplant itself is taken from the eye of a person who has died, after consent from the donor's family. Our goal is to improve the outcome for patients who require transplants of tissue to the front of the eye, in order to restore their vision or to relieve pain. Our work is predicated on the finding that unwanted immune responses are the major cause of graft failure in such patients. The recipient recognizes the grafted tissue as being foreign, and rejects it. Treatment with conventional systemic drugs appears to hold little promise for further improvements in outcome, but gene therapy applied to the donor tissue may provide a safe and effective way of reducing transplant failure. Gene therapy can be undertaken on the donor tissue in the laboratory, prior to transplantation surgery. In this project, we will assess the suitability of a new method of modifying the transplant. All of the work will be performed on the laboratory bench, or in experimental animals.Read moreRead less
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
Role For Sphingosine Kinase-1 In Endothelial Progenitor Cell Survival And Differentiation.
Funder
National Health and Medical Research Council
Funding Amount
$294,205.00
Summary
Lay description: Collectively, diseases of the vascular system contribute immensely to the burden of health care in Australia. Notably, abnormal blood vessel formation and function (angiogenesis) has been identified as a major cause or contributor to the vascular complications associated with inflammation, cancer, rheumatoid arthritis and diabetes. Endothelial cells are one of the principle cells of blood vessels forming a barrier between the blood and tissues. This project aims to understand th ....Lay description: Collectively, diseases of the vascular system contribute immensely to the burden of health care in Australia. Notably, abnormal blood vessel formation and function (angiogenesis) has been identified as a major cause or contributor to the vascular complications associated with inflammation, cancer, rheumatoid arthritis and diabetes. Endothelial cells are one of the principle cells of blood vessels forming a barrier between the blood and tissues. This project aims to understand the process whereby mature endothelial cells are formed and how replacement of damaged endothelial cells is normally achieved. Stem cell therapy is considered the new frontier for the treatment of many diseases. Understanding how endothelial progenitor cells differentiate to mature endothelial cells and the signals which operate inside the cell may allow therapeutic manipulation of key target moecules in order to limit or control inflammation, tumourigenesis, rheumatoid arthritis and diabetic retinopathy. Our results suggest that one target maybe the enzyme sphingosine kinase.Read moreRead less
Single-chain Antibodies For Directed Stem Cell Homing And Targeting Of Effector Cells In Vascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$596,677.00
Summary
Regenerative cellular therapy e.g. with adult stem cells is a promising novel medical therapy. However, until now there is no reliable method to direct cells to areas where they are needed. We aim to develop a biotechnological approach based on genetically tailored antibody molecules that will allow cell targeting. As a pilot project we will test whether this approach improves lipid deposition and hardening of arteries.
Hematopoietic Transplants From Autologous Pluripotent Cell Sources
Funder
National Health and Medical Research Council
Summary
This proposal investigates the utility of two types of patient-derived stem cells for transplantation into blood. These are induced pluripotent stem cells that are reprogrammed from specialized tissues such as skin cells, and stem cells derived using the genetic material of oocytes or sperm only ( one-parent embryos). Using the mouse, we are looking at the ability of these cells to form normal blood lineages after transplantation, and to repair blood in a mouse model for beta-thalassemia.
The Role Of Ap2a2 In Self-renewal Of Haematopoietic And Leukemic Stem Cells
Funder
National Health and Medical Research Council
Funding Amount
$579,171.00
Summary
The daily replenishment of the blood system is dependent on the blood stem cell. A unique property of these stem cells is self-renewal where the stem cell function is preserved, whilst other daughter cells continue to divide. Our research investigates the molecular mechanisms that regulate stem cell self-renewal. This work has potential clinical application on at least two levels: expansion of stem cells for transplantation, and for attacking abnormal cancer cell self-renewal pathways.
Role Of The Hypoxia-inducible Transcription Factor HIF-1a In Controlling Haematopoietic Stem Cell Fate
Funder
National Health and Medical Research Council
Funding Amount
$586,428.00
Summary
Haematopoietic stem cells (HSCs) reside in the bone marrow (BM) and make all immune and blood cells. We have found that, in the areas of the BM where HSC normally live, the level of oxygen is very low (hypoxia) and decreases even further when HSC are forced to move into the blood in order to be collected for transplantation. This project is to better understand how oxygenation of the BM controls HSC behaviour and properties, and to evaluate its impact on HSC transplantation.
Kidney Mesenchymal Stem Cells In Tubular Development, Repair And Turnover.
Funder
National Health and Medical Research Council
Summary
In Australia, 11.3% of deaths are associated with chronic kidney disease with >$1 billion per annum spent on treating this condition. At present, only dialysis and transplantation are available to treat end stage kidney disease. We have found a kidney stem cell population in both human and mouse that can form new epithelial structures. In this project, we will investigate the normal role played by these kidney stem cells and examine whether they can contribute to kidney regeneration.