MICA:The Potential of Multipoint Adult Progenitor Cells as a Novel Therapeutic Strategy in Alcoholic Hepatitis

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Liver disease accounts for one in ten of all deaths in people between the ages of 40 and 49 and costs the NHS £1 billion every year. Alcohol is a major cause of liver disease. One way in which alcoholic liver disease can present is alcoholic hepatitis, which is a very dramatic condition with a high mortality, despite current treatments. Therefore, we urgently need to find new treatments for this condition. Understanding the way in which alcohol results in alcoholic hepatitis can help us to identify potential targets for developing new treatments. Due to previous research, we know which types of cells are responsible for causing liver damage in alcoholic hepatitis. If we can find an effective way of reducing the numbers of these harmful cells getting into the liver, this can be possibly be used to treat alcoholic hepatitis. The most common cause of death in patients with alcoholic hepatitis is infection. Strengthening our body's response against infection is another way of reducing the number of deaths from alcoholic hepatitis.Several researchers have suggested that certain cells found in the bone marrow, called multipotent adult progenitor cells (MAPC), can help to reduce inflammation. In test-tube studies, animal studies and clinical trials, these cells have been shown to reduce the inflammation associated with a number of conditions, including heart attack and stroke. It has also been shown that bone marrow cells can improve the ability of cells to fight infection. After being injected in over 100 humans so far, it appears that MAPC injections are safe. However, it is unclear exactly how the MAPC work, or whether they could be used in treatment of alcoholic hepatitis. Testing the effectiveness and safety of treatments in mice before they are used in humans aims to minimise the risk of harm to patients. In our department, we have developed a method to induce alcoholic hepatitis in mice. Using human blood samples from alcoholic hepatitis patients, I can see if the findings in mice are comparable to those in humans, and therefore whether we can use the mouse experiments to accurately predict what will happen in humans.To assess the usefulness of MAPC in alcoholic hepatitis, I am then going to treat mice with these cells, and assess whether they reduce liver injury. Then I am going to do further experiments to investigate how these cells achieve their effect. For example, I am going to investigate whether MAPC prevent inflammatory cells from entering the liver, and determine exactly which molecules and cells are implicated in this. I will also be testing whether MAPC affect the ability to cells to clear infection. Using human cells in my laboratory work to supplement mouse experiments will help to ensure that my work will be applicable to humans. If we can define the exact mechanisms of action of MAPC, we can refine our treatments to maximise the intended benefits and minimise side effects. These studies will work together to help us to understand if MAPC can be used to treat alcoholic hepatitis and to find out the underlying mechanism.