Liver  - Development and Stem Cells

Function of the Liver:

The liver is the largest internal organ, which provides essential metabolic exocrinic and endocrinic functions. These include production of bile, metabolism of dietary compounds, detoxification, regulation of glucose levels through glycogen storage and control of blood homeostasis by secretion of clotting factors and serum proteins such as albumin.

Embryonic Development of the Liver:

The embryonic liver originates from the ventral foregut endoderm, which becomes the hepatic diverticulum, the first morphological sign of the embryonic liver.  The hepatic diverticulum is located adjacent to the developing heart and can be identified at E9.0. The anterior portion of the hepatic diverticulum gives rise to the liver and intrahepatic biliary tree, whereas the posterior portion forms the gall bladder and the extrahepatic bile ducts (EHBD). At E9.5, hepatoblasts delaminate from the anterior portion of the hepatic diverticulum and invade the adjacent septum transversum mesenchyme (STM) to form the liver bud. The STM contributes the fibroblasts and stellate cells of the liver. Between E9.5 and E15, the liver bud undergoes significant growth and, following invasion of hematopoietic cells, becomes the primary site of fetal haematopoiesis.

Hepatoblasts are bi-potential precursor cells which give rise to hepatocytes and biliary epithelial cells (BECs; also known as cholangyocytes), the two major liver cell types. Hepatocytes are parenchymal cells that comprise about 70% of hepatic cells. BECs line the lumen of the intrahepatic bile ducts (IHBD). The remaining 30% of the adult liver is comprised of non-parenchymal cells, including Kupffer cells, stromal cells and stellate cells of mesodermal origin.

The portal vein and hepatic artery, formed from segments of the vitelline and the umbilical veins of the fetus, are two major blood vessels that supply the liver. Within the adult liver, the bile duct, portal vein and hepatic artery run in parallel and form the ‘portal triad’. The portal triad is surrounded by hepatocytes arranged in single-cell sheets known as hepatic plates, separated by sinusoidal spaces that are connected to a network of capillaries. Blood plasma from the portal vein enters the sinusoidal space and comes into direct contact with the basal surface of hepatocytes, which absorb metabolites and toxins. Bile is secreted from the apical surface of the hepatocytes into the bile canaliculi (grooves in the cell surface), and then flows though IHBD to the EHBD, and into the gall bladder, where it is stored before release into the duodenum.