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

doi:10.1038/nbt1257

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 journal › Article › peer-review

191 Scopus citations

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 language	English (US)
Pages (from-to)	1412-1419
Number of pages	8
Journal	Nature biotechnology
Volume	24
Issue number	11
DOIs	https://doi.org/10.1038/nbt1257
State	Published - Nov 2006
Externally published	Yes

ASJC Scopus subject areas

Biotechnology
Bioengineering
Applied Microbiology and Biotechnology
Molecular Medicine
Biomedical Engineering

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Soto-Gutiérrez, A., Kobayashi, N., Rivas-Carrillo, J. D., Navarro-Álvarez, N., Zhao, D., Okitsu, T., Noguchi, H., Basma, H., Tabata, Y., Chen, Y., Tanaka, K., Narushima, M., Miki, A., Ueda, T., Jun, H. S., Yoon, J. W., Lebkowski, J., Tanaka, N., & 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

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

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

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.",

author = "Alejandro Soto-Guti{\'e}rrez and Naoya Kobayashi and Rivas-Carrillo, {Jorge David} and Nalu Navarro-{\'A}lvarez and Debaio Zhao and Teru Okitsu and Hirofumi Noguchi and Hesham Basma and Yashuhiko Tabata and Yong Chen and Kimiaki Tanaka and Michiki Narushima and Atsushi Miki and Tadayoshi Ueda and Jun, {Hee Sook} and Yoon, {Ji Won} and Jane Lebkowski and Noriaki Tanaka and Fox, {Ira J.}",

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AU - Tanaka, Kimiaki

AU - Narushima, Michiki

AU - Miki, Atsushi

AU - Ueda, Tadayoshi

AU - Jun, Hee Sook

AU - Yoon, Ji Won

AU - Lebkowski, Jane

AU - Tanaka, Noriaki

AU - Fox, Ira J.

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

Abstract

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