Instant hepatic differentiation of human embryonic stem cells using activin A and a deleted variant of HGF

Yong Chen, Alejandro Soto-Gutierrez, Nalu Navarro-Alvarez, Jorge David Rivas-Carrillo, Tomoki Yamatsuji, Yasuhiro Shirakawa, Noriaki Tanaka, Naoya Kobayashi

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Human embryonic stem (hES) cells have the ability to differentiate into a variety of different cell lineages and potentially provide a source of differentiated cells for many therapeutic uses. Here we investigated an efficient method of hepatic differentiation from hES cells. A human ES cell line, KhES-1, was used and maintained by a nonfeeder method. KhES-1 cells were cultured for 5 days in the presence of human activin A (50 ng/ml) and then treated with a deleted variant of hepatocyte growth factor (dHGF) at 0, 100, or 500 ng/ml for 7 days. The resultant cells were biologically analyzed. The expression of the endodermal genes SOX17 and FOXA2 increased in KhES-1 cells after activin A treatment. In contrast, Oct4, a self-renewal undifferentiated marker, decreased in a time-dependent manner in KhES-1 cells. Following a 7-day treatment of the resultant cells with dHGF, especially at 500 ng/ml, KhES-1 cells showed an expression of the hepatic makers albumin, AFP, and CK18. Transitional electron microscopy showed well-developed glycogen rosettes and a gap junction in KhES-1 cells treated with 500 ng/ml of dHGF. We developed an efficient method to differentiate KhES-1 cells into hepatocyte-like cells in vitro using 50 ng/ml of activin A and 500 ng/ml of dHGF.

Original languageEnglish (US)
Pages (from-to)865-871
Number of pages7
JournalCell Transplantation
Volume15
Issue number10
DOIs
StatePublished - 2006
Externally publishedYes

Fingerprint

Stem cells
Liver
Hepatocyte Growth Factor
Cells
Electron microscopy
Genes
activin A
Human Embryonic Stem Cells
Hepatocytes
Gap Junctions
Therapeutic Uses
Cell Lineage
Intercellular Signaling Peptides and Proteins
Glycogen
Albumins
Cultured Cells
Electron Microscopy
Gene Expression
Cell Line

Keywords

  • Differentiation
  • Hepatocyte
  • Hepatocyte growth factor
  • hES cells

ASJC Scopus subject areas

  • Cell Biology
  • Transplantation

Cite this

Chen, Y., Soto-Gutierrez, A., Navarro-Alvarez, N., Rivas-Carrillo, J. D., Yamatsuji, T., Shirakawa, Y., ... Kobayashi, N. (2006). Instant hepatic differentiation of human embryonic stem cells using activin A and a deleted variant of HGF. Cell Transplantation, 15(10), 865-871. https://doi.org/10.3727/000000006783981305

Instant hepatic differentiation of human embryonic stem cells using activin A and a deleted variant of HGF. / Chen, Yong; Soto-Gutierrez, Alejandro; Navarro-Alvarez, Nalu; Rivas-Carrillo, Jorge David; Yamatsuji, Tomoki; Shirakawa, Yasuhiro; Tanaka, Noriaki; Kobayashi, Naoya.

In: Cell Transplantation, Vol. 15, No. 10, 2006, p. 865-871.

Research output: Contribution to journalArticle

Chen, Y, Soto-Gutierrez, A, Navarro-Alvarez, N, Rivas-Carrillo, JD, Yamatsuji, T, Shirakawa, Y, Tanaka, N & Kobayashi, N 2006, 'Instant hepatic differentiation of human embryonic stem cells using activin A and a deleted variant of HGF', Cell Transplantation, vol. 15, no. 10, pp. 865-871. https://doi.org/10.3727/000000006783981305
Chen Y, Soto-Gutierrez A, Navarro-Alvarez N, Rivas-Carrillo JD, Yamatsuji T, Shirakawa Y et al. Instant hepatic differentiation of human embryonic stem cells using activin A and a deleted variant of HGF. Cell Transplantation. 2006;15(10):865-871. https://doi.org/10.3727/000000006783981305
Chen, Yong ; Soto-Gutierrez, Alejandro ; Navarro-Alvarez, Nalu ; Rivas-Carrillo, Jorge David ; Yamatsuji, Tomoki ; Shirakawa, Yasuhiro ; Tanaka, Noriaki ; Kobayashi, Naoya. / Instant hepatic differentiation of human embryonic stem cells using activin A and a deleted variant of HGF. In: Cell Transplantation. 2006 ; Vol. 15, No. 10. pp. 865-871.
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