Reversal of mouse hepatic failure using an implanted liver-assist device containing ES cell-derived hepatocytes

Alejandro Soto-Gutiérrez, Naoya Kobayashi, Jorge David Rivas-Carrillo, Nalu Navarro-Álvarez, Debaio Zhao, Teru Okitsu, Hirofumi Noguchi, Hesham Basma, Yashuhiko Tabata, Yong Chen, Kimiaki Tanaka, Michiki Narushima, Atsushi Miki, Tadayoshi Ueda, Hee Sook Jun, Ji Won Yoon, Jane Lebkowski, Noriaki Tanaka, Ira J. Fox

Research output: Contribution to journalArticle

173 Citations (Scopus)

Abstract

Severe acute liver failure, even when transient, must be treated by transplantation and lifelong immune suppression. Treatment could be improved by bioartificial liver (BAL) support, but this approach is hindered by a shortage of human hepatocytes. To generate an alternative source of cells for BAL support, we differentiated mouse embryonic stem (ES) cells into hepatocytes by coculture with a combination of human liver nonparenchymal cell lines and fibroblast growth factor-2, human activin A and hepatocyte growth factor. Functional hepatocytes were isolated using albumin promoter-based cell sorting. ES cell-derived hepatocytes expressed liver-specific genes, secreted albumin and metabolized ammonia, lidocaine and diazepam. Treatment of 90% hepatectomized mice with a subcutaneously implanted BAL seeded with ES cell-derived hepatocytes or primary hepatocytes improved liver function and prolonged survival, whereas treatment with a BAL seeded with control cells did not. After functioning in the BAL, ES cell-derived hepatocytes developed characteristics nearly identical to those of primary hepatocytes.

Original languageEnglish (US)
Pages (from-to)1412-1419
Number of pages8
JournalNature Biotechnology
Volume24
Issue number11
DOIs
StatePublished - Nov 2006
Externally publishedYes

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Liver Failure
Embryonic Stem Cells
Stem cells
Liver
Artificial Liver
Hepatocytes
Equipment and Supplies
Albumins
Cells
Hepatocyte Growth Factor
Acute Liver Failure
Fibroblast Growth Factor 2
Diazepam
Coculture Techniques
Lidocaine
Ammonia
Fibroblasts
Sorting
Transplantation
Genes

ASJC Scopus subject areas

  • Microbiology

Cite this

Soto-Gutiérrez, A., Kobayashi, N., Rivas-Carrillo, J. D., Navarro-Álvarez, N., Zhao, D., Okitsu, T., ... Fox, I. J. (2006). Reversal of mouse hepatic failure using an implanted liver-assist device containing ES cell-derived hepatocytes. Nature Biotechnology, 24(11), 1412-1419. https://doi.org/10.1038/nbt1257

Reversal of mouse hepatic failure using an implanted liver-assist device containing ES cell-derived hepatocytes. / Soto-Gutiérrez, Alejandro; Kobayashi, Naoya; Rivas-Carrillo, Jorge David; Navarro-Álvarez, Nalu; Zhao, Debaio; Okitsu, Teru; Noguchi, Hirofumi; Basma, Hesham; Tabata, Yashuhiko; Chen, Yong; Tanaka, Kimiaki; Narushima, Michiki; Miki, Atsushi; Ueda, Tadayoshi; Jun, Hee Sook; Yoon, Ji Won; Lebkowski, Jane; Tanaka, Noriaki; Fox, Ira J.

In: Nature Biotechnology, Vol. 24, No. 11, 11.2006, p. 1412-1419.

Research output: Contribution to journalArticle

Soto-Gutiérrez, A, Kobayashi, N, Rivas-Carrillo, JD, Navarro-Álvarez, N, Zhao, D, Okitsu, T, Noguchi, H, Basma, H, Tabata, Y, Chen, Y, Tanaka, K, Narushima, M, Miki, A, Ueda, T, Jun, HS, Yoon, JW, Lebkowski, J, Tanaka, N & Fox, IJ 2006, 'Reversal of mouse hepatic failure using an implanted liver-assist device containing ES cell-derived hepatocytes', Nature Biotechnology, vol. 24, no. 11, pp. 1412-1419. https://doi.org/10.1038/nbt1257
Soto-Gutiérrez A, Kobayashi N, Rivas-Carrillo JD, Navarro-Álvarez N, Zhao D, Okitsu T et al. Reversal of mouse hepatic failure using an implanted liver-assist device containing ES cell-derived hepatocytes. Nature Biotechnology. 2006 Nov;24(11):1412-1419. https://doi.org/10.1038/nbt1257
Soto-Gutiérrez, Alejandro ; Kobayashi, Naoya ; Rivas-Carrillo, Jorge David ; Navarro-Álvarez, Nalu ; Zhao, Debaio ; Okitsu, Teru ; Noguchi, Hirofumi ; Basma, Hesham ; Tabata, Yashuhiko ; Chen, Yong ; Tanaka, Kimiaki ; Narushima, Michiki ; Miki, Atsushi ; Ueda, Tadayoshi ; Jun, Hee Sook ; Yoon, Ji Won ; Lebkowski, Jane ; Tanaka, Noriaki ; Fox, Ira J. / Reversal of mouse hepatic failure using an implanted liver-assist device containing ES cell-derived hepatocytes. In: Nature Biotechnology. 2006 ; Vol. 24, No. 11. pp. 1412-1419.
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