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Hepatology International

Published in:

01-07-2013 | Original Article

Transdifferentiation of human fibroblasts into hepatocyte-like cells by defined transcriptional factors

Authors: Tomomi Kogiso, Hikaru Nagahara, Motoyuki Otsuka, Keiko Shiratori, Steven F. Dowdy

Published in: Hepatology International | Issue 3/2013

Abstract

Purpose

Liver transplantation is currently the only curative therapeutic option for end-stage liver cirrhosis. However, due to the limitations of donor liver availability and occasional rejection, it cannot always be successfully applied. In this study, we determined whether fibroblasts can be transdifferentiated into hepatocyte-like cells by transcription factors that initiate and maintain hepatocyte differentiation.

Methods

Fibroblasts were transduced with retrovirus vectors carrying FOXA2, HNF4α, and C/EBPβ. To enhance the efficiency of transdifferentiation, cMyc was also expressed.

Results

Transdifferentiation was successful using both neonatal fibroblasts and human forehead fibroblasts. The transdifferentiated cells produced hepatocyte-specific proteins such as albumin and cytochrome, and had important hepatocyte-specific functions, such as glycogen storage and indocyanine green uptake, suggesting that the cells function at least as partial hepatocytes.

Conclusions

These results provide a novel method of generating differentiated hepatocyte-like cells, and may represent an alternative source of cells for future cell-based therapeutics for end-stage liver diseases.

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Title: Transdifferentiation of human fibroblasts into hepatocyte-like cells by defined transcriptional factors
Authors: Tomomi Kogiso
Hikaru Nagahara
Motoyuki Otsuka
Keiko Shiratori
Steven F. Dowdy
Publication date: 01-07-2013
Publisher: Springer India
Published in: Hepatology International / Issue 3/2013
Print ISSN: 1936-0533
Electronic ISSN: 1936-0541
DOI: https://doi.org/10.1007/s12072-013-9432-5

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Abstract

Purpose

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