Liver Regeneration: Different Sub-Populations of Parenchymal Cells at Play Choreographed by an Injury-Specific Microenvironment

Int J Mol Sci. 2018 Dec 18;19(12):4115. doi: 10.3390/ijms19124115.

Abstract

Liver regeneration is crucial for the maintenance of liver functional mass during homeostasis and diseases. In a disease context-dependent manner, liver regeneration is contributed to by hepatocytes or progenitor cells. As long as they are replicatively competent, hepatocytes are the main cell type responsible for supporting liver size homeostasisand regeneration. The concept that all hepatocytes within the lobule have the same proliferative capacity but are differentially recruited according to the localization of the wound, or whether a yet to be defined sub-population of hepatocytes supports regeneration is still debated. In a chronically or severely injured liver, hepatocytes may enter a state of replicative senescence. In such conditions, small biliary cells activate and expand, a process called ductular reaction (DR). Work in the last few decades has demonstrated that DR cells can differentiate into hepatocytes and thereby contribute to parenchymal reconstitution. In this study we will review the molecular mechanisms supporting these two processes to determine potential targets that would be amenable for therapeutic manipulation to enhance liver regeneration.

Keywords: ductular reaction; hepatectomy, chronic liver injury, liver failure; hepatocytes; liver progenitor cells.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Differentiation / genetics*
  • Cell Lineage / genetics
  • Cell Lineage / physiology
  • Cellular Microenvironment / genetics
  • Hepatocytes / cytology
  • Hepatocytes / metabolism
  • Humans
  • Liver / growth & development*
  • Liver Regeneration / genetics*
  • Liver Regeneration / physiology
  • Parenchymal Tissue / cytology
  • Parenchymal Tissue / physiology
  • Stem Cells*