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

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.

journal_name

Cell Transplant

journal_title

Cell transplantation

authors

Chen Y,Soto-Gutierrez A,Navarro-Alvarez N,Rivas-Carrillo JD,Yamatsuji T,Shirakawa Y,Tanaka N,Basma H,Fox IJ,Kobayashi N

doi

10.3727/000000006783981305

subject

Has Abstract

pub_date

2006-01-01 00:00:00

pages

865-71

issue

10

eissn

0963-6897

issn

1555-3892

journal_volume

15

pub_type

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