Efficient generation of hepatocyte-like cells from human induced pluripotent stem cells

Cell Res. 2009 Nov;19(11):1233-42. doi: 10.1038/cr.2009.107. Epub 2009 Sep 8.

Abstract

Human induced pluripotent stem (iPS) cells are similar to embryonic stem (ES) cells, and can proliferate intensively and differentiate into a variety of cell types. However, the hepatic differentiation of human iPS cells has not yet been reported. In this report, human iPS cells were induced to differentiate into hepatic cells by a stepwise protocol. The expression of liver cell markers and liver-related functions of the human iPS cell-derived cells were monitored and compared with that of differentiated human ES cells and primary human hepatocytes. Approximately 60% of the differentiated human iPS cells at day 7 expressed hepatic markers alpha fetoprotein and Alb. The differentiated cells at day 21 exhibited liver cell functions including albumin Asecretion, glycogen synthesis, urea production and inducible cytochrome P450 activity. The expression of hepatic markers and liver-related functions of the iPS cell-derived hepatic cells were comparable to that of the human ES cell-derived hepatic cells. These results show that human iPS cells, which are similar to human ES cells, can be efficiently induced to differentiate into hepatocyte-like cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation*
  • Cell Line
  • Cells, Cultured
  • Cytochrome P-450 Enzyme System / metabolism
  • Embryonic Stem Cells / cytology*
  • Embryonic Stem Cells / metabolism
  • Glycoproteins / metabolism
  • Hepatocytes / cytology*
  • Hepatocytes / metabolism
  • Humans
  • Induced Pluripotent Stem Cells* / cytology
  • Induced Pluripotent Stem Cells* / metabolism
  • Liver Glycogen / biosynthesis
  • Serum Albumin / metabolism
  • Serum Albumin, Human
  • Urea / metabolism
  • alpha-Fetoproteins / biosynthesis

Substances

  • ALB protein, human
  • Glycoproteins
  • Liver Glycogen
  • Serum Albumin
  • alpha-Fetoproteins
  • Urea
  • Cytochrome P-450 Enzyme System
  • Serum Albumin, Human