Cellular Cross-talk Between Liver Progenitor Cells And Hepatic Stellate Cells Is Required For Hepatic Fibrogenesis
Funder
National Health and Medical Research Council
Funding Amount
$618,517.00
Summary
Deloitte Access Economics data proposes the total economic burden of liver disease in Australia in 2012 was >$50 billion. This study will identify how the liver heals itself by inducing liver cell populations which interact to regenerate damaged liver tissue in chronic liver disease. This knowledge may lead to the development of novel therapeutic interventions for the treatment of liver scarring and liver cancer, and to assist in normal liver regeneration following chronic liver disease.
Role Of Human Amnion Epithelial Cells In Resolving Hepatic Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$618,755.00
Summary
When the liver is injured repeatedly by viruses and alcohol, it responds through a wound healing process that can lead to extensive scar tissue in the liver (cirrhosis). This condition may require liver transplantation and lifelong use of drugs to prevent the body from rejecting the new organ. To develop an alternate therapy, we will study if substances secreted by amnion cells from the human placenta (afterbirth), which would normally be discarded, can reduce liver scar tissue in mice .
The Role Of The Glutamine Transporter SNAT3 In Ion Transport, Cell Signaling And Ammonia Detoxification
Funder
National Health and Medical Research Council
Funding Amount
$393,249.00
Summary
Hepatic encephalopathy is a syndrome observed in patients with liver cirrhosis and is caused by increased amounts of ammonia in the blood. The proposed project investigates a transporter that is involved in ammonia and glutamine metabolism in liver and brain. The two organs are critical to the pathology of liver failure and ammonia toxicity resulting from reduced liver function. The transporter thus could become a drug target for a variety of liver diseases.
I am a hepatology scientist investigating the mechanisms associated with the development of hepatic fibrosis and cirrhosis in chronic liver diseases affecting children (cystic fibrosis liver disease and biliary atresia) and adults (haemochromatosis).
A Pilot Study To Evaluate The Safety Of Intravenously Administered Human Amnion Epithelial Cells In Patients With Compensated Cirrhosis
Funder
National Health and Medical Research Council
Funding Amount
$394,692.00
Summary
We propose a first-in-man clinical trial of human amnion epithelial cells (hAEC), a stem cell from the placenta, to assess safety in patients with stable liver cirrhosis. Worldwide, cirrhosis is the 6th most common cause of death. Liver transplantation remains the only chance for survival for some people with cirrhosis. In animal models, hAEC can substantially reduce liver scar tissue. Our goal is to develop hAEC as a therapy to reduce the need for liver transplantation.
Does Immunosuppression Affect The Post-transplantation Hepatic Fibrogenic Response?
Funder
National Health and Medical Research Council
Funding Amount
$360,000.00
Summary
Liver transplantation is often the only treatment option for patients who progress to end-stage liver disease after initial treatment has failed. Unfortunately, re-emergence of disease is common and patients often develop fibrosis and cirrhosis (scarring of the liver) in the donor organ. In some cases it has been observed that this scarring often develops rapidly, sometimes in a year or less following transplantation. Re-transplantation is often required. This differs from the usual progression ....Liver transplantation is often the only treatment option for patients who progress to end-stage liver disease after initial treatment has failed. Unfortunately, re-emergence of disease is common and patients often develop fibrosis and cirrhosis (scarring of the liver) in the donor organ. In some cases it has been observed that this scarring often develops rapidly, sometimes in a year or less following transplantation. Re-transplantation is often required. This differs from the usual progression of cirrhosis pre-transplant which often takes years or decades to develop. While essential to prevent rejection of the transplanted organ, immunosuppression is not without side effects. To date, few studies have examined the effect of immunosuppressive agents on the development of hepatic fibrosis and the key fibrosis effector cell type, the hepatic stellate cell. These reports have shown that one of the most commonly used immunosuppressant agents (FK-506) may adversely influence fibrosis progression while rapamycin may prevent fibrosis progression. However little is known regarding the mechanisms through which this occurs. We propose to examine the effect of four different immunosuppressants on fibrosis development both in vitro and in vivo to determine whether scar development or scar breakdown pathways are altered post-immunosuppression. If the factors driving the fibrogenesis in the transplanted organ can be elucidated it may then be possible to develop therapeutic strategies to tackle the problem. This may result in a reduced need for re-transplantation which has obvious benefits to the transplant patient but would also reduce the numbers of donor organs required.Read moreRead less