Optimising Islet Transplantation With Vascularized Tissue Engineering Chambers
Funder
National Health and Medical Research Council
Funding Amount
$451,651.00
Summary
Diabetics have high blood sugar levels because cells in the pancreas known as islets produce too little of the hormone insulin. Most diabetics need daily insulin injections to maintain normal blood sugar levels. Transplanting islets is the most promising way to treat type 1 diabetes, but, apart from the obvious difficulty of rejection of foreign islets, several major problems remain: (1) there are insufficient pancreata (and therefore islets) for transplantation; and (2) the efficiency of delive ....Diabetics have high blood sugar levels because cells in the pancreas known as islets produce too little of the hormone insulin. Most diabetics need daily insulin injections to maintain normal blood sugar levels. Transplanting islets is the most promising way to treat type 1 diabetes, but, apart from the obvious difficulty of rejection of foreign islets, several major problems remain: (1) there are insufficient pancreata (and therefore islets) for transplantation; and (2) the efficiency of delivery of surviving islet transplants is too low. In pilot studies we have grown a new living pancreatic organ in mice by inserting islets from genetically-related mice together with a structural protein matrix, growth factors and blood vessels inside a plastic chamber. The blood vessels maintain nutrition to the islet cells and simultaneously allow insulin to be released into the bloodstream, thus normalising the high blood sugar in diabetics. In Aim 1 of these experiments we will find the optimal way to grow mature islets in blood vessel-containing chambers in diabetic mice, focusing on (a) the best time to add islets to the chamber - 0, 1 or 2 weeks after establishment, (b) the minimum number of islets to effectively normalise blood sugar and (c) how long we can keep islets alive and functional in chambers, examining periods up to 12 months. In Aim 2 we will test the ability of islet stem cells (provided by our co-investigators at Walter and Eliza Hall Institute, Melbourne) to survive in the chambers and to produce sufficient insulin to effectively lower blood sugar levels to normal in diabetic mice. In Aim 3 we will grow human islets in chambers in special diabetic mice that do not reject foreign tissue, in order to confirm similar behaviour of human islets in this controlled environment. Using this data, we hope to create a research model of functioning islets, that is accessible, retrievable and manipulable, for the further study of diabetes and transplantation.Read moreRead less
Evaluation A Novel Vitronectin:growth Factor Complex For Treatment Of Chronic Venous Leg Ulcers
Funder
National Health and Medical Research Council
Funding Amount
$854,975.00
Summary
Chronic leg ulcers in the elderly are an important problem, diminshing quality of life and costing at least A$1 billion per year. New treatments are urgently required. This study will test a new topical growth factor therapy designed to have greatly improved activity in wounds.The project is a collaboration between scientists and doctors at the Queensland Univeristy of Technology and the University of Western Australia. Many wound types may ultimately benefit from this treatment.
Susceptibility To Venous Leg Ulceration: Investigation Of The First Genetic Risk Factor
Funder
National Health and Medical Research Council
Funding Amount
$291,000.00
Summary
This application aims to confirm our preliminary identification of the first candidate gene as a risk factor for developing venous leg ulceration. Since patients with venous leg ulcers experience pain and psychological consequences including anger and depression, all of which impact negatively on quality of life, active prevention of ulceration will have significant lifestyle and financial benefits. Venous leg ulcers occur in patients who have venous disease, in particular in patients with previ ....This application aims to confirm our preliminary identification of the first candidate gene as a risk factor for developing venous leg ulceration. Since patients with venous leg ulcers experience pain and psychological consequences including anger and depression, all of which impact negatively on quality of life, active prevention of ulceration will have significant lifestyle and financial benefits. Venous leg ulcers occur in patients who have venous disease, in particular in patients with previous deep vein thrombosis. However, not all patients with a deep vein thrombosis or other forms of venous disease will go on to develop a venous ulcer. Our preliminary results show that patients with a venous ulcer have a greater frequency of this gene than healthy controls without venous ulcers, and suggest that patients with the candidate gene have a greater risk of developing venous ulceration. In this study we aim to determine whether the gene itself contributes to ulcer susceptibility or whether it is just a marker of that susceptibility. We can do this by assessing related genes and the levels of the protein produced by this gene. In this study we also aim to assess whether patients with a proven deep vein thrombosis are more likely to develop venous ulceration if they have the candidate gene. These studies have the potential to lead to the development of a diagnostic screening test for use in patients with venous disease, to assess the likelihood of developing leg ulceration. This will enable more active treatment to prevent leg ulceration. If this gene contributes to ulcer susceptibility new specific treatments may be developed for ulcer management and prevention.Read moreRead less
Preconditioning: The Molecular Basis For Protection From Hepatic Ischemia-reperfusion Injury
Funder
National Health and Medical Research Council
Funding Amount
$406,980.00
Summary
When the blood supply to the liver is cut off temporarily (ischemia) and later restored (reperfusion) the liver is damaged by a process called ischemia-reperfusion (IR) injury. This is a major problem during liver surgery and is also an underlying problem in liver transplantation; following storage of a donor liver ready for placing into the recipient it can undergo a similar process called preservation injury. We now understand a lot about how IR comes about, particularly by the formation of da ....When the blood supply to the liver is cut off temporarily (ischemia) and later restored (reperfusion) the liver is damaged by a process called ischemia-reperfusion (IR) injury. This is a major problem during liver surgery and is also an underlying problem in liver transplantation; following storage of a donor liver ready for placing into the recipient it can undergo a similar process called preservation injury. We now understand a lot about how IR comes about, particularly by the formation of damaging oxygen radicals within liver cells to start a process of programmed cell death, but it remains difficult to prevent or treat IR injury. A recent breakthrough has been recognition that subjecting the liver to only a short period (5 or 10 minutes) of ischemia protects against a later period of prolonged ischemia or IR. In the investigator s mouse model, for example, such preconditioning was 60 to 90% protective (depending on the time after IR). This project seeks to understand how preconditioning works to protect the liver against IR injury. Our idea is that preconditioning generates a limited amount of oxygen radicals, and that these turn on signalling pathways in the cell that regulate certain protective genes. Genes that encode antioxidant and other anti-stress pathways are likely to be important, but so are genes that prepare the cell to enter the cell cycle and divide into new cells that regenerate the liver. Conversely, genes that program cell death may be turned off. The outcomes of this research will be to understand the molecular and cellular basis of how preconditioning protects against ischemia-reperfusion injury of the liver. This will allow drug treatments to be devised that, by simulating preconditioning, prevent this common and severe type of liver damage.Read moreRead less