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Review
. 2015 Oct;149(4):876-882.
doi: 10.1053/j.gastro.2015.08.004. Epub 2015 Aug 14.

Liver Stem Cells: Experimental Findings and Implications for Human Liver Disease

George K Michalopoulos #  1 , Zahida Khan #  2
Affiliations
Review

Liver Stem Cells: Experimental Findings and Implications for Human Liver Disease

George K Michalopoulos et al. Gastroenterology. 2015 Oct.

Abstract

Evidence from human histopathology and experimental studies with rodents and zebrafish has shown that hepatocytes and cholangiocytes may function as facultative stem cells for each other in conditions of impaired regeneration. The interpretation of the findings derived from these studies has generated considerable discussion and some controversies. This review examines the evidence obtained from the different experimental models and considers implications that these studies may have for human liver disease.

Keywords: Cholangiocytes; Hepatocytes; Liver Progenitor Cell; Liver-Specific Tissue Stem Cells; Transdifferentiation.

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Figures

Figure 1
Figure 1. Regenerative clusters of mixed phenotypes in fulminant hepatic failure
Regenerative clusters composed of cholangiocytes (green arrows) organized in tortuous ductules surrounding and connecting with hepatocytes (red arrows). Hepatocytes express EPCAM, a marker of cholangiocytes, to various degrees. EPCAM expression decreases towards the center of the regenerative cluster. These features are frequently observed in histologic analyses of liver tissues from patients with fulminant hepatic failure with massive hepatocyte necrosis and ductular reaction.
Figure 2
Figure 2. Potential mechanisms of liver regeneration in relation to parenchymal cell injury
Following partial hepatectomy (PHx), most liver cells are capable of regeneration, with hepatocytes and cholangiocytes respectively contributing to self-replication (center panel). Under extreme hepatocyte loss, such as in cases of fulminant hepatic failure or AAF exposure, cholangiocytes become progenitor cells that become hepatocytes (left panel). With biliary injury (following administration of DAPM), hepatocytes undergo transdifferentiation directly into cholangiocytes (right panel). These types of reprograming events result in phenotypic inter-conversion to replace the injured cell type, and involve a number of regenerative pathways including HGF signaling via MET, and EGFR signaling.
See this image and copyright information in PMC

References

    1. Demetris AJ, Seaberg EC, Wennerberg A, et al. Ductular reaction after submassive necrosis in humans. Special emphasis on analysis of ductular hepatocytes. Am J Pathol. 1996;149:439–48. - PMC - PubMed
    1. Desmet V, Roskams T, Van Eyken P. Ductular reaction in the liver. Pathol Res Pract. 1995;191:513–24. - PubMed
    1. Butler SL, Dong H, Cardona D, et al. The antigen for Hep Par 1 antibody is the urea cycle enzyme carbamoyl phosphate synthetase 1. Lab Invest. 2008;88:78–88. - PubMed
    1. Gracz AD, Fuller MK, Wang F, et al. Brief report: CD24 and CD44 mark human intestinal epithelial cell populations with characteristics of active and facultative stem cells. Stem Cells. 2013;31:2024–30. - PMC - PubMed
    1. Verfaillie CM. Biliary cells to the rescue of Prometheus. Gastroenterology. 2014;146:611–4. - PubMed