Hepatic progenitors for liver disease: current position

Abstract

Liver regeneration restores the original functionality of hepatocytes and cholangiocytes in response to injury. It is regulated on several levels, with different cellular populations contributing to this process, eg, hepatocytes, liver precursor cells, intrahepatic stem cells. In response to injury, mature hepatocytes have the capability to proliferate and give rise to new hepatocytes and cholangiocytes. Meanwhile, liver precursor cells (oval cells) have become the most recognized bipotential precursor cells in the damaged liver. They rapidly proliferate, change their cellular composition, and differentiate into hepatocytes and cholangiocytes to compensate for the cellular loss and maintain liver homeostasis. There is a growing body of evidence that oval cells originate from the intrahepatic stem cell(s), which in turn give(s) rise to epithelial, including oval cells, and/or other hepatic cells of nonepithelial origin. Since there is a close relationship between the liver and hematopoiesis, bone marrow derived cells can also contribute to liver regeneration by the fusion of myeloid cells with damaged hepatocytes, or differentiation of mesenchymal stem cells into hepatocyte-like cells. The current review discusses the contribution of different cells to liver regeneration and their characteristics.

Keywords: cholangiocytes; hepatic progenitor; hepatocytes; intrahepatic stem cells; liver disease; liver precursor cells; oval cells.

Figure 1

Cells contributing to liver regeneration. Notes: Different cellular types regulate liver regeneration on several levels. Contribution of mature hepatocytes to regeneration of hepatic parenchymal cells is shown in black. Liver precursor cells with bipotential differentiation capacity are shown in red. Proposed pathways of liver regeneration, which require further clarification, are shown in grey. Abbreviations: HSC, hepatic stem cells; MSC, mesenchymal stem cells.

Figure 2

Markers of oval cells. Notes: intracellular and surface markers of oval cells in rats and mice differ from liver precursor cells (LPCs) in humans. The most compelling markers that are potentially useful for isolation of oval cells in different species, are shown.