Differentiation and Transplantation of Human Embryonic Stem Cell-Derived Hepatocytes

Hesham E Basma, Alejandro Soto-Gutiérrez, Govardhana Rao Yannam, Liping Liu, Ryotaro Ito, Toshiyuki Yamamoto, Ewa Ellis, Steven D Carson, Shintaro Sato, Yong Chen, David Muirhead, Nalu Navarro-Álvarez, Ronald J. Wong, Jayanta Roy-Chowdhury, Jeffrey L. Platt, David F Mercer, John D. Miller, Stephen C. Strom, Naoya Kobayashi, Ira J. Fox

Research output: Contribution to journalArticle

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Abstract

Background & Aims: The ability to obtain unlimited numbers of human hepatocytes would improve the development of cell-based therapies for liver diseases, facilitate the study of liver biology, and improve the early stages of drug discovery. Embryonic stem cells are pluripotent, potentially can differentiate into any cell type, and therefore could be developed as a source of human hepatocytes. Methods: To generate human hepatocytes, human embryonic stem cells were differentiated by sequential culture in fibroblast growth factor 2 and human activin-A, hepatocyte growth factor, and dexamethasone. Functional hepatocytes were isolated by sorting for surface asialoglycoprotein-receptor expression. Characterization was performed by real-time polymerase chain reaction, immunohistochemistry, immunoblot, functional assays, and transplantation. Results: Embryonic stem cell-derived hepatocytes expressed liver-specific genes, but not genes representing other lineages, secreted functional human liver-specific proteins similar to those of primary human hepatocytes, and showed human hepatocyte cytochrome P450 metabolic activity. Serum from rodents given injections of embryonic stem cell-derived hepatocytes contained significant amounts of human albumin and α1-antitrypsin. Colonies of cytokeratin-18 and human albumin-expressing cells were present in the livers of recipient animals. Conclusions: Human embryonic stem cells can be differentiated into cells with many characteristics of primary human hepatocytes. Hepatocyte-like cells can be enriched and recovered based on asialoglycoprotein-receptor expression and potentially could be used in drug discovery research and developed as therapeutics.

Original languageEnglish (US)
Pages (from-to)990-999.e4
JournalGastroenterology
Volume136
Issue number3
DOIs
StatePublished - Mar 2009

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Hepatocytes
Transplantation
Embryonic Stem Cells
Asialoglycoprotein Receptor
Liver
Drug Discovery
Albumins
Human Embryonic Stem Cells
Keratin-18
Hepatocyte Growth Factor
Fibroblast Growth Factor 2
Cell- and Tissue-Based Therapy
Cytochrome P-450 Enzyme System
Dexamethasone
Genes
Liver Diseases
Real-Time Polymerase Chain Reaction
Rodentia
Immunohistochemistry
Injections

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

Cite this

Basma, H. E., Soto-Gutiérrez, A., Yannam, G. R., Liu, L., Ito, R., Yamamoto, T., ... Fox, I. J. (2009). Differentiation and Transplantation of Human Embryonic Stem Cell-Derived Hepatocytes. Gastroenterology, 136(3), 990-999.e4. https://doi.org/10.1053/j.gastro.2008.10.047

Differentiation and Transplantation of Human Embryonic Stem Cell-Derived Hepatocytes. / Basma, Hesham E; Soto-Gutiérrez, Alejandro; Yannam, Govardhana Rao; Liu, Liping; Ito, Ryotaro; Yamamoto, Toshiyuki; Ellis, Ewa; Carson, Steven D; Sato, Shintaro; Chen, Yong; Muirhead, David; Navarro-Álvarez, Nalu; Wong, Ronald J.; Roy-Chowdhury, Jayanta; Platt, Jeffrey L.; Mercer, David F; Miller, John D.; Strom, Stephen C.; Kobayashi, Naoya; Fox, Ira J.

In: Gastroenterology, Vol. 136, No. 3, 03.2009, p. 990-999.e4.

Research output: Contribution to journalArticle

Basma, HE, Soto-Gutiérrez, A, Yannam, GR, Liu, L, Ito, R, Yamamoto, T, Ellis, E, Carson, SD, Sato, S, Chen, Y, Muirhead, D, Navarro-Álvarez, N, Wong, RJ, Roy-Chowdhury, J, Platt, JL, Mercer, DF, Miller, JD, Strom, SC, Kobayashi, N & Fox, IJ 2009, 'Differentiation and Transplantation of Human Embryonic Stem Cell-Derived Hepatocytes', Gastroenterology, vol. 136, no. 3, pp. 990-999.e4. https://doi.org/10.1053/j.gastro.2008.10.047
Basma, Hesham E ; Soto-Gutiérrez, Alejandro ; Yannam, Govardhana Rao ; Liu, Liping ; Ito, Ryotaro ; Yamamoto, Toshiyuki ; Ellis, Ewa ; Carson, Steven D ; Sato, Shintaro ; Chen, Yong ; Muirhead, David ; Navarro-Álvarez, Nalu ; Wong, Ronald J. ; Roy-Chowdhury, Jayanta ; Platt, Jeffrey L. ; Mercer, David F ; Miller, John D. ; Strom, Stephen C. ; Kobayashi, Naoya ; Fox, Ira J. / Differentiation and Transplantation of Human Embryonic Stem Cell-Derived Hepatocytes. In: Gastroenterology. 2009 ; Vol. 136, No. 3. pp. 990-999.e4.
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AU - Soto-Gutiérrez, Alejandro

AU - Yannam, Govardhana Rao

AU - Liu, Liping

AU - Ito, Ryotaro

AU - Yamamoto, Toshiyuki

AU - Ellis, Ewa

AU - Carson, Steven D

AU - Sato, Shintaro

AU - Chen, Yong

AU - Muirhead, David

AU - Navarro-Álvarez, Nalu

AU - Wong, Ronald J.

AU - Roy-Chowdhury, Jayanta

AU - Platt, Jeffrey L.

AU - Mercer, David F

AU - Miller, John D.

AU - Strom, Stephen C.

AU - Kobayashi, Naoya

AU - Fox, Ira J.

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