The quest for liver progenitor cells: A practical point of view

Schematic representation of the two regenerative pathways involved in liver repair. In normal circumstances, the regeneration/recovery of the liver is driven by the fully differentiated hepatocyte compartment (left side). After a short period of time parenchymal and non-parenchymal cells have restored the hepatic mass and functions. When hepatocytes are impaired, blocked or the growth is overwhelmed by severe injury (right side), the liver progenitor cell compartment (LPC) (light blue) will take over. Once activated, these cells proliferate (yellow arrows) and give rise to bipotential transit-amplifying cells or oval cells and their progeny (dark blue). In rodents, these oval cells emerge from the periportal zone (close to bile ducts, BD), give rise to cords of oval cells that infiltrate along the liver plate, and then differentiate into hepatocytes and cholangiocytes to rescue the liver.

Schematic representation of the cellular complexity of the liver. Two major epithelial cell types constitute this organ: hepatocytes and cholangiocytes (or bile duct cells). Kupffer cells, sinusoidal cells, stellate cells, myofibroblasts and fibroblasts are resident liver cells. The bile produced by hepatocytes is initially secreted into the bile canaliculi, which are located between the cytoplasmic membranes of two adjacent hepatocytes. Bile canaliculi are connected with bile ducts (BD) through the interposition of the canal of Hering (CoH) (the niche of the liver progenitor cells). Terminal branches of the portal vein (PV) and hepatic artery (HA) converge and mix as they enter sinusoids in the liver. The blood flows through the sinusoids and empties into the central vein (CV) of each lobule. The locations of hepatocytes, liver sinusoidal cells, extracellular matrix, basal membrane and hepatic stellate cells are well defined. All these cells could interact and cross-talk with the liver progenitor cells.

Different approaches used to isolate and characterize LPCs from rodents. Different solutions can be use to enrich the LPCs obtained by digestion/perfusion of the liver: Percoll, OptiPrep, Nycodenz or Ficoll-gradient. Characterization of the obtained cells can be done at different levels of purity/complexity or on total liver.