Further Development 20.2: Diffferentiation of the Cells of the Liver

The two major liver cell types are the hepatocytes (liver cells) and the cholangiocytes that form the cells of the bile ducts (see Figure 20.2). Paracrine factors of the TGF-β family as well as Notch signaling from the blood vessels appear to stimulate the production of the duct cells, while glucocorticoid hormones and other paracrine factors (hepatocyte growth factor and Wnts) help specify the hepatocytes (Schmidt et al. 1995; Clotman et al. 2005). In addition, there are other cells in the liver, including the liver sinusoidal endothelial cells. These are specialized endodermal cells that create the blood channels in the liver (Goldman et al. 2014). These cells are critical for liver functioning, as they bring nutrients and poisonous substances into the liver to be metabolized and degraded. Sinusoidal endothelial cells also appear to play a critical role in liver regeneration, since they are the source of two paracrine factors—hepatocyte growth factor and angiopoietin-2—that are critical for the organized division of hepatoblast stem cells (Ding et al. 2010; DeLeve 2013; Hu et al. 2014). The ability of the mammalian liver to regenerate has been a fascinating topic, since it grows back only the same amount of liver tissue as was removed or destroyed. We are just beginning to understand how our body accomplishes this, and we will return to discuss liver regeneration more fully in Chapter 22.