P53 And Hepatocyte Proliferation In Chronic Liver Disease
Funder
National Health and Medical Research Council
Funding Amount
$331,360.00
Summary
The aim of this project is understand how loss of control of p53, a tumour suppressor gene, in liver cells causes the transformation of normal liver cell (hepatocyte) to ‘rouge’ pre-cancerous cells in hepatocellular carcinoma (HCC) or primary liver cancer. We will test novel therapies to restore p53 function in liver cells in order to prevent or retard the development of HCC in patients with cirrhosis and those ‘at risk’ of this rapidly increasing fatal cancer in Australia.
ALCOHOL AND IMPAIRED LIVER REGENERATION: EFFECTS ON MITOGENIC SIGNALING PATHWAYS
Funder
National Health and Medical Research Council
Funding Amount
$365,295.00
Summary
Patients who regularly consume alcohol are slow to recover from liver injury because alcohol poisons the liver's capacity to regenerate itself (grow back). Hence patients with alcohol-induced liver disease have a high mortality and prolonged hospital stays. The applicants have been supported by NHMRC to study how alcohol impairs liver regeneration. They found that the effect is at the level of cell surface receptors for the growth factors that control liver regeneration. Alcohol alters the funct ....Patients who regularly consume alcohol are slow to recover from liver injury because alcohol poisons the liver's capacity to regenerate itself (grow back). Hence patients with alcohol-induced liver disease have a high mortality and prolonged hospital stays. The applicants have been supported by NHMRC to study how alcohol impairs liver regeneration. They found that the effect is at the level of cell surface receptors for the growth factors that control liver regeneration. Alcohol alters the function of these receptors. One major discovery has been that it damages the capacity to generate a rise in calcium within the cell, something that is fundamentally required for any cell to divide and reproduce itself. Thus when a rise in calcium was produced artificially (with chemicals to unlock the internal calcium stores), liver cells from alcohol-fed rats once more responded normally under the influence of growth factors and replicated themselves. The present work isdesigned to find out where this effect of calcium is exerted. The investigators believe that it is related to how other types of signals work, the so-called protein kinase pathways. These are cascades of one protein turning on (activating) the next down the line to ultimately switch on the genes that control cell growth. They will manipulate liver cells from alcohol-fed rats in culture to establish which of these pathways is most affected, and which is the most critical for the control of cell division genes. These studies will greatly advance our understanding about how alcohol impairs liver regeneration. They will give new insight into the control of liver cell growth and division that is such a crucial response of the liver to injury, vital for survival of the liver. This kind of knowledge will open the door for new treatments to be designed that can control liver growth - turn it back on when it has been poisoned, or turn it off when it is inappropriately vigorous and predisposing to liver cancer.Read moreRead less
The Role Of TNF And Its Receptor Family In Liver Progenitor Cell Proliferation And Differentiation
Funder
National Health and Medical Research Council
Funding Amount
$250,500.00
Summary
Maintaining liver function is essential for health, and compromising this ultimately results in death. The liver is unusual, as it can regenerate to replace lost or damaged tissue. Recently it has been established that there are two pathways to liver regeneration. One involves hepatocytes, and this is normally associated with acute liver damage. The other, involves liver progenitor cells; and this is usually observed when there is chronic and severe liver damage, particularly when the proliferat ....Maintaining liver function is essential for health, and compromising this ultimately results in death. The liver is unusual, as it can regenerate to replace lost or damaged tissue. Recently it has been established that there are two pathways to liver regeneration. One involves hepatocytes, and this is normally associated with acute liver damage. The other, involves liver progenitor cells; and this is usually observed when there is chronic and severe liver damage, particularly when the proliferation of hepatocytes is impaired. This study seeks to understand the underlying mechanisms which recruit liver progenitor cells for regeneration. This knowledge can lead to strategies to augment the oval cell contribution to liver regeneration in cases of chronic liver damage, to enhance survival of the patient. It can be applied to strategies to grow and maintain liver stem cells in culture for the purpose of cell and gene therapy to correct liver dysfunction. It is also necessary to identify factors which affect oval cells and understand their mechanism of action because of their link to liver cancer. Oval cells have a Jekyll and Hyde characteristic, and it is important to know what leads them towards liver differentiation and regeneration, and what makes them produce liver cancers.Read moreRead less
When Prometheus Needs A Hand – How Human Amnion Epithelial Cells Resolve Fibrosis And Regenerate The Liver
Funder
National Health and Medical Research Council
Funding Amount
$530,653.00
Summary
Cirrhosis can progress to end stage disease for which transplantation provides the only hope for survival. Liver donors in Australia are scarce; the need for donor organs is increasing. Using stem cells to repair and regenerate damaged liver may provide an alternative to organ transplantation. We are studying placental stem cells that can decrease inflammation and increase progenitor cells to repair and regenerate liver. Our goal is to use these stem cells as treatment for human liver disease
Development Of Functional Liver Tissue Engineered From Murine Hepatocyte Or Liver Progenitor Cell Spheroids To Correct Liver Disease
Funder
National Health and Medical Research Council
Funding Amount
$459,482.00
Summary
Many patients suffering from severe liver disease require a liver transplant, but due to a shortage of liver donors, many die prior to liver transplantation. This study investigates novel methods of growing liver tissue from mature liver cells called hepatocytes, or, liver stem cells implanted in a plastic chamber in mice with acute and chronic liver disease. It is anticipated that new liver tissue will grow in the chamber, the mice will be cured, and that this technique can be translated to hum ....Many patients suffering from severe liver disease require a liver transplant, but due to a shortage of liver donors, many die prior to liver transplantation. This study investigates novel methods of growing liver tissue from mature liver cells called hepatocytes, or, liver stem cells implanted in a plastic chamber in mice with acute and chronic liver disease. It is anticipated that new liver tissue will grow in the chamber, the mice will be cured, and that this technique can be translated to humans with liver disease.Read moreRead less
Optimising Human Vascularisation And Liver Tissue Engineering Models To Develop Functional Bio-artificial Human Liver Tissue
Funder
National Health and Medical Research Council
Funding Amount
$124,761.00
Summary
This project aims to grow human blood vessels and liver cells derived from human stem cells within a supporting scaffold to generate a “liver in a dish”. Transplantation involves connecting blood vessels in this structure to those of the recipient. This should restore function in mice with human-like liver disease, thereby demonstrating potential of this technology to be developed as an alternative to liver transplantation.
Liver damage after liver surgery or shock is called ischemia-reperfusion injury (IRI). Recovery after surgical removal of liver tissue is due to liver regeneration. IRI and liver regeneration are controlled by specialised proteins called cytokines, one of which, TRAIL, is essential for both IRI and liver regeneration. This research is to find out how TRAIL exerts such seemingly opposite effects. The aim is to learn how to protect the liver against damage, and to stimulate its recovery.
Role Of TNF-á In Growth, Lineage Commitment And Differentiation Of Liver Progenitor Cells
Funder
National Health and Medical Research Council
Funding Amount
$228,589.00
Summary
The infection rate of HBV is 20% in Chinese and 10% in Australian in particularly aboriginal. The end-point of this disease is development liver failure and need functional replacement of the liver. Cell therapy represents an alternative of liver transplantation owing to shortage of organ. The information derived from this study is essential for developing strategies to promote growth and differentiation of liver progenitor cell both in vivo and in vitro for therapies to treat liver diseases.
Optimizing Implanted Cell Survival Using A Tissue Engineering Model
Funder
National Health and Medical Research Council
Funding Amount
$589,175.00
Summary
Cell therapy and tissue engineering involve the insertion of specific cells into damaged tissues or into a bioraector in a patient's body to generate new replacement tissues. This project seeks to improve two factors associated with inserting cells : 1. The innate survival characteristics of the cells being inserted, and 2. The blood vessel supply at the site of insertion. These techniques will greatly improve the survival of inserted cells.