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Am J Pathol. 2014 Feb;184(2):332-47. doi: 10.1016/j.ajpath.2013.09.026. Epub 2013 Nov 21.

Human induced pluripotent stem cells in hepatology: beyond the proof of concept.

Author information

1
INSERM, U1087, Montpellier, France; UMR 1040, Université Montpellier 1, Montpellier, France.
2
INSERM, U1087, Montpellier, France; UMR 1040, Université Montpellier 1, Montpellier, France; Hepato-Gastroenterology Service B, Saint Eloi Hospital, CHU Montpellier, Montpellier, France.
3
INSERM, UMR 1087, the Institute of the Thorax, Nantes, France; CNRS, UMR 6291, Nantes, France; School of Medicine, University of Nantes, Nantes, France.
4
INSERM, UMR 1087, the Institute of the Thorax, Nantes, France; CNRS, UMR 6291, Nantes, France; School of Medicine, University of Nantes, Nantes, France. Electronic address: karim.si-tayeb@univ-nantes.fr.

Abstract

The discovery of the wide plasticity of most cell types means that it is now possible to produce virtually any cell type in vitro. This concept, developed because of the possibility of reprogramming somatic cells toward induced pluripotent stem cells, provides the opportunity to produce specialized cells that harbor multiple phenotypical traits, thus integrating genetic interindividual variability. The field of hepatology has exploited this concept, and hepatocyte-like cells can now be differentiated from induced pluripotent stem cells. This review discusses the choice of somatic cells to be reprogrammed by emergent new and nonintegrative strategies, as well as the application of differentiated human induced pluripotent stem cells in hepatology, including liver development, disease modeling, host-pathogen interactions, and drug metabolism and toxicity. The actual consensus is that hepatocyte-like cells generated in vitro present an immature phenotype. Currently, developed strategies used to resolve this problem, such as overexpression of transcription factors, mimicking liver neonatal and postnatal modifications, and re-creating the three-dimensional hepatocyte environment in vitro and in vivo, are also discussed.

PMID:
24269594
DOI:
10.1016/j.ajpath.2013.09.026
[Indexed for MEDLINE]
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