title: Transdifferentiation of human fibroblasts into hepatocyte-like cells by defined transcriptional factors.
abstract: OBJECTIVE
  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.
authors.affiliation: Institute of Gastroenterology, Department of Internal Medicine, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan. kogiso@ige.twmu.ac.jp.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Kogiso
authors.affiliation: Aoyama Hospital, Tokyo Women's Medical University, 2-7-13 Kita-Aoyama, Minato-ku, Tokyo, 107-0061, Japan.
authors.forename: Hikaru
authors.initials: H
authors.lastname: Nagahara
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Otsuka
authors.affiliation: Institute of Gastroenterology, Department of Internal Medicine, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Shiratori
authors.affiliation: Department of Cellular and Molecular Medicine, UCSD School of Medicine, 9500 Gilman Drive, La Jolla, CA, 92093-0686, USA.
authors.forename: Steven F
authors.initials: SF
authors.lastname: Dowdy
keywords: C/EBPβ; FOXA2; HNF4α; Transcription factors; Transdifferentiation