Hepatic stem cells: from inside and outside the liver?

Abstract

The liver is normally proliferatively quiescent, but hepatocyte loss through partial hepatectomy, uncomplicated by virus infection or inflammation, invokes a rapid regenerative response from all cell types in the liver to perfectly restore liver mass. Moreover, hepatocyte transplants in animals have shown that a certain proportion of hepatocytes in foetal and adult liver can clonally expand, suggesting that hepatoblasts/hepatocytes are themselves the functional stem cells of the liver. More severe liver injury can activate a potential stem cell compartment located within the intrahepatic biliary tree, giving rise to cords of bipotential transit amplifying cells (oval cells), that can ultimately differentiate into hepatocytes and biliary epithelial cells. A third population of stem cells with hepatic potential resides in the bone marrow; these haematopoietic stem cells may contribute to the albeit low renewal rate of hepatocytes, but can make a more significant contribution to regeneration under a very strong positive selection pressure. In such instances, cell fusion rather than transdifferentiation appears to be the underlying mechanism by which the haematopoietic genome becomes reprogrammed.

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].…”

“…More severe liver injury, particularly longstanding iterative injury (eg chronic viral hepatitis) or when replicative senescence ensues (eg steatohepatitis), activates a facultative stem cell compartment located within the intrahepatic biliary tree, giving rise to cords of bipotential transit amplifying cells (named oval cells in rodents and hepatic progenitor cells in man) that can ultimately differentiate into hepatocytes and biliary epithelial cells [2]. A third population of stem cells with hepatic potential resides in the bone marrow; these stem cells usually make little contribution to regeneration but, after fusing with metabolically defective hepatocytes, can be reprogrammed to contribute in a major way to restoring liver function [3][4][5].…”

Comparative study of technique to obtain stem cells from bone marrow collection between the iliac crest and the femoral epiphysis in rabbits

“…They have two very important characteristics: self-renewal and differentiation potential. Furthermore, stem cells from different organs and tissues (heart, liver, brain, bone marrow, muscles, spleen) can be derived and propagated in vitro 11,12,13,14 .…”

Thermoreversible gelation polymer induces the emergence of hepatic stem cells in the partially injured rat liver

“…[3][4][5] "Oval cells" or "ductular hepatocytes" are involved in the ductular reaction in rodents. 5,6 These cells may be derived from putative stem cells and may differentiate into hepatocytes; (3) Bone marrow-derived cells may participate in hepatic regeneration. 4,5,7 Here we report that, in the hepatic regeneration of focal injury by TGP, ductular reactions are initially induced, and hepatic stem cells involved in the ductules may differentiate into hepatocytes.…”

“…[3][4][5] Surviving hepatocytes immediately proliferate and restore the original mass 4 ; (2) When the proliferation of hepatocytes is inhibited by some toxins such as 2-acetylaminofluorene, hepatic growth stimulation results in emergent ductules, and the cells in the ductules gradually migrate into the hepatic parenchyma. [3][4][5] "Oval cells" or "ductular hepatocytes" are involved in the ductular reaction in rodents. 5,6 These cells may be derived from putative stem cells and may differentiate into hepatocytes; (3) Bone marrow-derived cells may participate in hepatic regeneration.…”