Defining the functional role of the progenitor cell-laminin interaction during liver regeneration

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Liver cirrhosis is the fifth most common cause of death in the UK. Any cause of chronic liver injury(e.g. viruses, fat, alcohol, inherited disorders) can result in scarring and eventually lead to cirrhosisand liver cancer. At present, the only effective treatment for cirrhosis is liver transplantation but many patients die whilst waiting for a new liver.In the adult, many organs possess their own ‘stem cells‘ which are able to replenish stocks of cellsas they are depleted. As the cirrhotic liver‘s ‘stem cells‘, termed oval cells in rodents, proliferate to regenerate the injured liver, they are surrounded by a specific matrix component called laminin. We know from other organs (such as the brain) that the interactions between the adult stem cell and laminin are critical for regeneration.I will examine the liver stem cell-laminin relationship using rodent models of liver injury and using cultured liver cells.Understanding the regulation of liver stem cells will be essential to rationally design newtreatments for liver disease.