Liver stem cells: when the going gets tough they get going

Abstract

The ability of the liver to regenerate is widely acknowledged, and this is usually accomplished by the entry of normally proliferatively quiescent hepatocytes into the cell cycle. However, when hepatocyte regeneration is impaired, small bile ducts proliferate and invade into the adjacent hepatocyte parenchyma. In humans and experimental animals these ductal cells are referred to as oval cells, and their association with defective regeneration has led to the belief that they are the progeny of facultative stem cells. Oval cells are of great biological interest since they may represent a target population for hepatic carcinogens, and they may also be useful vehicles for ex vivo gene therapy for the correction of inborn errors of metabolism. The ability of oval cells to differentiate into hepatocytes has been demonstrated unequivocally. However, this process only occurs when the regenerative capacity of hepatocytes is overwhelmed, and thus, unlike the intestinal epithelium, the liver is not behaving as a classical continually renewing stem cell‐fed lineage.

Expression of matrilin-2 in oval cells during rat liver regeneration

“…The oval cells are the progenies of the hepatic stem cell compartment, which is activated when the hepatocytes are unable to regenerate the liver mass (Alison et al, 1997;Petersen et al, 1998;Forbes et al, 2002). Contrary to most of the terminally differentiated epithelial cells, there is no structured basement membrane around the hepatocytes.…”

Stem cells in liver regeneration, fibrosis and cancer: the good, the bad and the ugly

“…In both humans [62] and mice [63], the extent of this reaction is dependent on the severity of the damage. This so-called 'oval cell' or 'ductular reaction' amplifies a cholangiocytederived (biliary) population before these cells differentiate into either hepatocytes or cholangiocytes [2,[64][65][66][67]. Oval cells are derived from the canal of Hering, and in rodents this canal barely extends beyond the limiting plate ( Figures 4, 5); in contrast, in human liver the organization of the biliary tree is different, with the canal of Hering extending to the proximate third of the lobule [68] and so apparently requiring a name change from oval cells to 'hepatic progenitor cells' (HPCs) [69].…”

The Fox Genes in the Liver: From Organogenesis to Functional Integration

“…When liver injury is severe or chronic, or when hepatocyte proliferation is blocked experimentally in animal models, small bipotential progenitors are activated (2,18,49,50,56,118,168,169,180). These cells, termed "oval cells" or "intermediate hepatobiliary cells," are small and have a high nuclear-to-cytoplasmic ratio, and cannot be detected in the quiescent liver (161).…”