Activation and regulation of reserve liver progenitor cells

The mammalian liver possesses an extraordinary capacity for regeneration of tissue mass and cell numbers following loss of hepatocytes due to partial tissue loss (surgical resection) or hepatotoxic injury (necrosis). Restoration of liver mass can be obtained through the outgrowth and expansion of a number of different cell types depending upon the nature and extent of injury and/or tissue deficit. In an otherwise healthy liver, the replacement of hepatocytes (and tissue mass) is achieved through the proliferation of differentiated, normally quiescent hepatocytes contained in the residual (viable) tissue. However, in certain forms of liver injury, the capacity of differentiated hepatocytes to proliferate in response to liver tissue deficit is significantly impaired. When this occurs, reserve stem-like progenitor cells are activated to proliferate and replace lost hepatocytes. In this review, we will discuss the currently available information regarding the activation and outgrowth of each of these liver progenitor cell populations.