Liver Regeneration in Health and Disease

In a healthy liver, the rate of cell turnover is very low; nevertheless regeneration of acutely lost modest amounts of parenchymal tissue is rapidly accomplished by the proliferation of normally quiescent hepatocytes. Hepatocytes are “primed” to enter the cell cycle by a number of cytokines and microRNAs, while many growth factors are implicated in “driving” proliferation. However, most liver disease presents as either acute liver failure or more chronic forms of injury (e.g., alcoholic fatty liver disease [AFLD], viral hepatitis, metabolic liver disease) where iterative injury has induced a state of hepatocyte senescence, thus necessitating the activation and mobilization of a potential stem cell population located within the intrahepatic biliary tree. Activation of these bipotential hepatic progenitor cells (HPCs) from the canal of Hering seems crucial for patient survival after acute forms of massive liver damage, and we are …