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Sci Rep. 2015 Oct 27;5:15706. doi: 10.1038/srep15706.

Generation of integration-free induced hepatocyte-like cells from mouse fibroblasts.

Author information

1
Department of Stem Cell Biology, School of Medicine, Konkuk University, 1 Hwayang-dong, Gwangjin-gu, Seoul 143-701, Republic of Korea.
2
Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Röntgenstrasse 20, 48149 Münster, Germany.
3
REBIRTH Cluster of Excellence, Hannover Medical School, Hannover 30625, Germany.
4
University of Münster, Medical Faculty, Domagkstrasse 3, 48149 Münster, Germany.
5
KU Open-Innovation Center, Institute of Biomedical Science &Technology, Konkuk University, 1 Hwayang-dong, Gwangjin-gu, Seoul 143-701, Republic of Korea.

Abstract

The ability to generate integration-free induced hepatocyte-like cells (iHeps) from somatic fibroblasts has the potential to advance their clinical application. Here, we have generated integration-free, functional, and expandable iHeps from mouse somatic fibroblasts. To elicit this direct conversion, we took advantage of an oriP/EBNA1-based episomal system to deliver a set of transcription factors, Gata4, Hnf1a, and Foxa3, to the fibroblasts. The established iHeps exhibit similar morphology, marker expression, and functional properties to primary hepatocytes. Furthermore, integration-free iHeps prolong the survival of fumarylacetoacetate-hydrolase-deficient (Fah(-/-)) mice after cell transplantation. Our study provides a novel concept for generating functional and expandable iHeps using a non-viral, non-integrating, plasmid-based system that could facilitate their pharmaceutical and biomedical application.

PMID:
26503743
PMCID:
PMC4621602
DOI:
10.1038/srep15706
[Indexed for MEDLINE]
Free PMC Article

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