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

肝硬化是英国第五大最常见的死亡原因。慢性肝损伤的任何原因（例如病毒，脂肪，酒精，遗传性疾病）都可能导致疤痕，最终导致癌症和肝癌。目前，肝硬化的唯一有效治疗方法是肝移植，但许多患者在等待新肝脏时死亡。在成年人中，许多器官拥有自己的“干细胞”，能够在细胞耗尽时补充细胞储备。当坏死肝脏的“干细胞”，在啮齿动物中被称为卵圆细胞，增殖以再生受损的肝脏时，它们被称为层粘连蛋白的特定基质成分包围。我们从其他器官（如大脑）中了解到，成体干细胞和层粘连蛋白之间的相互作用对于再生至关重要。我将使用啮齿动物肝损伤模型和培养的肝细胞来检查肝干细胞和层粘连蛋白之间的关系。了解肝干细胞的调节对于合理设计肝病的新疗法至关重要。

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.