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Kogiso T, Nagahara H, Otsuka M, et al. Transdifferentiation of human fibroblasts into hepatocyte-like cells by defined transcriptional factors. Hepatol Int. 2013;7(3):937-44doi: 10.1007/s12072-013-9432-5.
Kogiso, T., Nagahara, H., Otsuka, M., Shiratori, K., & Dowdy, S. F. (2013). Transdifferentiation of human fibroblasts into hepatocyte-like cells by defined transcriptional factors. Hepatology international, 7(3), 937-44. https://doi.org/10.1007/s12072-013-9432-5
Kogiso, Tomomi, et al. "Transdifferentiation of human fibroblasts into hepatocyte-like cells by defined transcriptional factors." Hepatology international vol. 7,3 (2013): 937-44. doi: https://doi.org/10.1007/s12072-013-9432-5
Kogiso T, Nagahara H, Otsuka M, Shiratori K, Dowdy SF. Transdifferentiation of human fibroblasts into hepatocyte-like cells by defined transcriptional factors. Hepatol Int. 2013 Jul;7(3):937-44. doi: 10.1007/s12072-013-9432-5. Epub 2013 Mar 13. PMID: 26201932.
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Hepatol Int. 2013 Jul;7(3):937-44. doi: 10.1007/s12072-013-9432-5. Epub 2013 Mar 13.

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

Hepatology international

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

Affiliations

  1. Institute of Gastroenterology, Department of Internal Medicine, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan. [email protected].
  2. Aoyama Hospital, Tokyo Women's Medical University, 2-7-13 Kita-Aoyama, Minato-ku, Tokyo, 107-0061, Japan.
  3. Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
  4. Institute of Gastroenterology, Department of Internal Medicine, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan.
  5. Department of Cellular and Molecular Medicine, UCSD School of Medicine, 9500 Gilman Drive, La Jolla, CA, 92093-0686, USA.

PMID: 26201932 DOI: 10.1007/s12072-013-9432-5

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.

Keywords: C/EBPβ; FOXA2; HNF4α; Transcription factors; Transdifferentiation

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