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 Scopus citations

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 - Dec 1 2006

Keywords

  • Differentiation
  • Hepatocyte
  • Hepatocyte growth factor
  • hES cells

ASJC Scopus subject areas

  • Biomedical Engineering
  • Cell Biology
  • Transplantation

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    Chen, Y., Soto-Gutierrez, A., Navarro-Alvarez, N., Rivas-Carrillo, J. D., 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, 15(10), 865-871. https://doi.org/10.3727/000000006783981305