Neural Transplantation Of Human Bone Marrow Stromal Cells To Replace Oligodendrocytes Lost In Multiple Sclerosis
Funder
National Health and Medical Research Council
Funding Amount
$249,750.00
Summary
Multiple sclerosis is a disease of the central nervous system in which myelin (an insulative coating around the axons of neurons) and oligodendrocytes (the cells that produce myelin) are attacked and damaged by an unknown process. This damage is referred to as demyelination and results in a blocking or weakening of nerve signal conduction. Some of the symptoms of multiple sclerosis are weakness, tingling or numbness of limbs, and double vision or visual loss. One strategy to repair the demyelina ....Multiple sclerosis is a disease of the central nervous system in which myelin (an insulative coating around the axons of neurons) and oligodendrocytes (the cells that produce myelin) are attacked and damaged by an unknown process. This damage is referred to as demyelination and results in a blocking or weakening of nerve signal conduction. Some of the symptoms of multiple sclerosis are weakness, tingling or numbness of limbs, and double vision or visual loss. One strategy to repair the demyelination is to transplant cells into the damaged brain that can replace the damaged oligodendrocytes and remyelinate. Studies have shown that oligodendrocyte progenitor cells and neural stem cells transplanted into the brain can mature into oligodendrocytes and myelinate axons. However these cells are very difficult to obtain, the best source is foetal terminations but the use of such tissue raises ethical and practical problems. Recently cells found in adult bone marrow, called marrow stromal cells, have been shown to differentiate into neural cells when transplanted into the brain. This raises the possibility that sufferers of multiple sclerosis may be able to have marrow stromal cells taken from their bone marrow and then transplanted into their brains to replace their damaged oligodendrocytes. Our study will investigate the differentiation of marrow stromal cells into oligodendrocytes and determine if marrow stromal cells transplanted into demyelinated mouse brain can replace damaged oligodendrocytes and remyelinate areas of damage.Read moreRead less
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
Tolerogenic Dendritic Cells In Common Marmoset Renal Transplantation
Funder
National Health and Medical Research Council
Funding Amount
$162,756.00
Summary
ORGAN TRANSPLANT PATIENTS currently need life-long immune suppressing drugs to prevent rejection, often using 15 medications a day, costing Australia $52M in 2002. These drugs increase risks of infection and cancer. 90% of patients develop some form of cancer over 30 years. They also cause non-specific side effects including high blood pressure, diabetes and osteoporosis. The average lifespan of a kidney transplant is 8-15 years. Major causes of kidney transplant loss are rejection and drug toxi ....ORGAN TRANSPLANT PATIENTS currently need life-long immune suppressing drugs to prevent rejection, often using 15 medications a day, costing Australia $52M in 2002. These drugs increase risks of infection and cancer. 90% of patients develop some form of cancer over 30 years. They also cause non-specific side effects including high blood pressure, diabetes and osteoporosis. The average lifespan of a kidney transplant is 8-15 years. Major causes of kidney transplant loss are rejection and drug toxicity. TRANSPLANTS ARE REJECTED when a recipient's immune system sees the kidney as foreign. Immune suppressing drugs prevent rejection by stopping the reaction to foreign tissues, but this causes increased infection and cancer risk. IMMUNE TOLERANCE means the recipient's immune system sees a transplant not as foreign but as part of itself, no longer reacting to it. If tolerance could be achieved for transplants, patients wouldn't need to use immune suppressing drugs. Costs of immune suppression would be nil. Tolerance is the best long-term solution for patients needing transplants. Tolerance has been achieved in various ways in mice models. DENDRITIC CELLS can be used to induce tolerance as they can silence a recipient's immune system, preventing it from seeing transplant tissues as foreign. We have shown in mice that a single infusion of a certain type of dendritic cells caused prolonged transplant tolerance without needing immune suppression. This project aims to use dendritic cells to induce tolerance in a marmoset model - a required step before allowing this therapy to be done in humans. PRIMATES like MARMOSETS have close genetic identity to humans and are ideal transplant models as their immune systems react much more like humans than other animals. Marmosets are not an endangered species and are smaller, cheaper and easier to care for than other primates. Ultimately, experiments in other species would need repeating in primates before human trials could be done.Read moreRead less
Elucidating The Mechanism Of IL-2 Cytokine/antibody Mediated Transplantation Tolerance
Funder
National Health and Medical Research Council
Funding Amount
$624,429.00
Summary
Organ transplantation is a life-saving treatment for end-stage organ failure. However, patients must take immunosuppressive drugs to prevent rejection, a lifetime of which increases the risk of infection and cancer. An alternative to drugs is to manipulate the immune system from within. We discovered a way to boost the immune ‘regulators’ so that they stifle the graft-destroying response. We are optimising this approach with the aim of transplanting organs without long-term immunosuppression.
Stem Cell Engineering To Establish Tolerance And Reverse Autoimmunity
Funder
National Health and Medical Research Council
Funding Amount
$497,250.00
Summary
The immune system is designed to protect us from harmful invaders such as bacteria, viruses and parasites. It should not attack our own tissues. However, in certain individuals, the immune system does attack our own tissues leading to life threatening conditions such as diabetes, multiple sclerosis and rheumatoid arthritis. To date, there is no cure for autoimmune diseases. Treatment is designed to treat the destructive effects of the disease. A strategy for achieving a cure is to program the im ....The immune system is designed to protect us from harmful invaders such as bacteria, viruses and parasites. It should not attack our own tissues. However, in certain individuals, the immune system does attack our own tissues leading to life threatening conditions such as diabetes, multiple sclerosis and rheumatoid arthritis. To date, there is no cure for autoimmune diseases. Treatment is designed to treat the destructive effects of the disease. A strategy for achieving a cure is to program the immune system to remove the harmful immune cells. Autoimmune gastritis which leads to pernicious anaemia is an autoimmune disease which affects the acid secreting cells of the stomach. To get a better understanding of autoimmune diseases, animal models are often used. We use a number of mouse models of autoimmune gastritis which closely resembles the human disease and thus makes a very good working model. Using these models we are exploring novel techniques aimed at reversing or curing established disease. This relies on removing the disease causing cells from the body and re-programming the immune system so as not to produce these cells.Read moreRead less
Therapeutic Potential Of Peritoneal Mononuclear Phagocytes From Peritoneal Dialysis Patients
Funder
National Health and Medical Research Council
Funding Amount
$375,817.00
Summary
Mononuclear phagocytes (MP) are key cells which are now being used to treat various diseases. In Australia, more than 10 million end stage kidney disease(ESKD) patients are treated with chronic dialysis, and more than 20% of them are on peritoneal dialysis (PD). Each PD patient discards more than 20 million MP in dialysate daily. We will explore the possibility of using these MP to treat diseases including transplant rejection.
Cross-reactive Anti-viral T Cells Mediate Allograft Rejection In Lung Transplantation.
Funder
National Health and Medical Research Council
Funding Amount
$379,563.00
Summary
In solid organ transplantation chronic viral infections can play a major role in causing graft dysfunction and-or loss. This study investigates the role of a specific population of immunological cells. These specific anti-viral immune cells are key controllers of viral infections and have also been implicated in mediating the destruction and-or rejection of a transplanted graft.
The Menstrual Cycle, Menopause And Gender Specific Health Needs Of Women With Complex Medical And Psychiatric Conditions.
Funder
National Health and Medical Research Council
Funding Amount
$149,982.00
Summary
The great advances in medical science mean that women are living longer, sometimes with very complex conditions.The aim of this study is to determine how common women’s health issues are in women who have had a lung or bone marrow transplant and in women with severe mental illness. The study will involve face to face interview with women and then a survey of a larger number of women. The study will help improve the care and quality of life of women who already face significant health challenges.