Cell therapy from bench to bedside: Hepatocytes from fibroblasts - the truth and myth of transdifferentiation

World J Gastroenterol. 2015 Jun 7;21(21):6427-33. doi: 10.3748/wjg.v21.i21.6427.


Hepatocyte transplantation is an alternative to liver transplantation in certain disorders such as inherited liver diseases and liver failure. It is a relatively less complicated surgical procedure, and has the advantage that it can be repeated several times if unsuccessful. Another advantage is that hepatocytes can be isolated from partly damaged livers which are not suitable for liver transplantation. Despite these advantages hepatocyte transplantation is less popular. Important issues are poor engraftment of the transplanted cells and the scarcity of donor hepatocytes. Generation of "hepatocyte like cells"/iHeps from embryonic stem cells (ES) and induced pluripotent stem cells (iPSCs) by directed differentiation is an emerging solution to the latter issue. Direct conversation or trans-differentiation of fibroblasts to "hepatocyte like cells" is another way which is, being explored. However this method has several inherent and technical disadvantages compared to the directed differentiation from ES or iPSC. There are several methods claiming to be "highly efficient" for generating "highly functional" "hepatocyte like cells". Currently different groups are working independently and coming up with differentiation protocols and each group claiming an advantage for their protocol. Directed differentiation protocols need to be designed, compared, analyzed and tweaked systematically and logically than empirically. There is a need for a well-coordinated global initiative comparable to the Human Genome Project to achieve this goal in the near future.

Keywords: Cell therapy; Embryonic stem cells; Fibroblasts; Gene therapy; Hepatocyte like cells; Hepatocyte transplantation; Induced pluripotent stem cells; Inherited/genetic liver disease; Telomere/telomerase; Trans differentiation; differentiation; i-Heps.

Publication types

  • Editorial
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Cell Transdifferentiation*
  • Fibroblasts / metabolism
  • Fibroblasts / physiology*
  • Hepatocytes / metabolism
  • Hepatocytes / physiology*
  • Hepatocytes / transplantation*
  • Humans
  • Liver Diseases / pathology
  • Liver Diseases / physiopathology
  • Liver Diseases / surgery*
  • Liver Regeneration
  • Models, Animal
  • Phenotype
  • Pluripotent Stem Cells / physiology
  • Translational Research, Biomedical / methods*


  • Biomarkers