The plastic liver: differentiated cells, stem cells, every cell?
Christopher J. Hindley, … , Gianmarco Mastrogiovanni, Meritxell Huch
Christopher J. Hindley, … , Gianmarco Mastrogiovanni, Meritxell Huch
Published December 1, 2014; First published November 17, 2014
Citation Information: J Clin Invest. 2014;124(12):5099-5102. https://doi.org/10.1172/JCI78372.
View: Text | PDF
Category: Commentary

The plastic liver: differentiated cells, stem cells, every cell?

Abstract

The liver is capable of full regeneration following several types and rounds of injury, ranging from hepatectomy to toxin-mediated damage. The source of this regenerative capacity has long been a hotly debated topic. The damage response that occurs when hepatocyte proliferation is impaired is thought to be mediated by oval/dedifferentiated progenitor cells, which replenish the hepatocyte and ductal compartments of the liver. Recently, reports have questioned whether these oval/progenitor cells truly serve as the facultative stem cell of the liver following toxin-mediated damage. In this issue of the JCI, Kordes and colleagues use lineage tracing to follow transplanted rat hepatic stellate cells, a resident liver mesenchymal cell population, in hosts that have suffered liver damage. Transplanted stellate cells repopulated the damaged rat liver by contributing to the oval cell response. These data establish yet another cell type of mesenchymal origin as the progenitor for the oval/ductular response in the rat. The lack of uniformity between different damage models, the extent of the injury to the liver parenchyma, and potential species-specific differences might be at the core of the discrepancy between different studies. Taken together, these data imply a considerable degree of plasticity in the liver, whereby several cell types can contribute to regeneration.

Authors

Christopher J. Hindley, Gianmarco Mastrogiovanni, Meritxell Huch

×

Figure 1

Schematic representation of cell regeneration in the liver after damage.

Options: View larger image (or click on image) Download as PowerPoint
Schematic representation of cell regeneration in the liver after damage....
(A) Partial hepatectomy or toxic injury activates hepatocytes and BECs, which are able to regenerate by self-duplication in all vertebrates studied. (B) Liver regeneration in mouse models after toxic injury. Lineage tracing in mice has demonstrated a contribution of both hepatocytes and BECs (at low frequencies) to the generation of progenitor and oval cells after damage (reviewed in ref. 6). (C) The work of Kordes et al. (12) suggests a role for HSCs in the repair process after toxic injury in the rat, joining BECs as a potential source of progenitor cells. Transdifferentiation of hepatocytes into BECs has been observed in the rat after bile duct ligation coupled with biliary toxin methylene diamiline (DAPM) pretreatment (27). (D) Activation of BECs to a progenitor state has been observed after toxic injury and 95% hepatocyte loss in the zebrafish liver (20). (E) The human liver can recover from fulminant liver failure that can cause up to 80% hepatocyte loss. A strong ductular reaction is observed, with 30% of the cells expressing markers of BEC and hepatocyte lineages. BECs seem to be involved in the regeneration process; however, it cannot be formally proved whether BECs generate hepatocytes. Further studies are needed to understand whether this process occurs through direct transdifferentiation or generation of a progenitor cell (11).