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Harnessing liver progenitors in the treatment of liver fibrosis: a step in the right direction?
  1. Katja Breitkopf-Heinlein1,
  2. Wing-Kin Syn2,3,4
  1. 1Division of Translational Hepatology, Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim, Heidelberg, Germany
  2. 2Division of Gastroenterology and Hepatology, Medical University of South Carolina, Charleston, South Carolina, USA
  3. 3Section of Gastroenterology, Ralph H Johnson Veteran Affairs Medical Center, Charleston, South Carolina, USA
  4. 4Department of Physiology, Faculty of Medicine and Nursing, University of Basque Country UPV/EHU, Leioa, Spain
  1. Correspondence to Dr Wing-Kin Syn, Division of Gastroenterology and Hepatology, Medical University of South Carolina, Charleston, SC 29425-2503, USA; synw{at}musc.edu

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Liver fibrosis is a leading cause of morbidity and mortality worldwide, and the prevalence of chronic liver disease is expected to increase in parallel with obesity and type 2 diabetes mellitus epidemics.1 As there is currently no Food and Drug Administration (FDA)-approved drug treatment for liver fibrosis, a liver transplant is the only curative treatment for a minority of individuals who develop cirrhosis-associated complications such as liver cancer and liver failure. In the face of an acute organ shortage, there is a growing impetus to better understand the precise cellular and molecular mechanisms of adult liver repair and regeneration, so that clinically relevant therapeutic targets can be identified.

In adults, after an acute liver injury, ‘normal’ regeneration occurs through the proliferation and expansion of remaining healthy hepatocytes and cholangiocytes, and there is minimal involvement of liver progenitors. By contrast, repair during chronic liver injury involves the proliferation of progenitor cells and cells with certain stem-like properties to differentiate into both hepatocytes and cholangiocytes, and thus support the restoration of liver function.2 3 What are the identity and/or origin of these liver progenitors? Multiple progenitor markers have been proposed, but none are completely specific as recent studies demonstrate that liver progenitors are actually a heterogeneous population that contains a variety of cell types, ranging from more primitive progenitors to more differentiated cells (eg, hepatocyte-like). Indeed, in adult mice, progenitors include biliary-like cells (also known as ‘oval cells’ in rodents) which arise in the ductal region, as well as progenitors around the central vein, de-differentiated hepatocytes or cholangiocytes, as well as multipotent mesenchymal stem cells (MSC) which also exhibit immunomodulatory properties.3 4 Similar …

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Footnotes

  • Contributors Both KB and W-KS contributed equally to this manuscript.

  • Funding KB was supported by funding from the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation—project no.:393225014; 394046768-SFB1366).

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Commissioned; internally peer reviewed.

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