In vitro differentiation of mouse ES cells into hepatocytes with coagulation factors VIII and IX expression profiles

Sci China C Life Sci. 2006 Jun;49(3):259-64. doi: 10.1007/s11427-006-0259-3.

Abstract

Coagulation factors II, V, VII, VIII, IX and X are produced by hepatocytes. So factors VIII and IX deficiencies, which result in hemophilia A and B, have the potential to respond to cellular replacement therapy. Embryonic stem (ES) cells provide a unique source for therapeutic applications. Here, E14 mouse ES cells have been induced into hepatocytes in vitro. Morphology revealed that ES-derived hepatic-like cells were round or polyhedral shaped with distinct boundary of individual cells, and some arranged in trabeculae. These cells expressed endodermal- or liver-specific mRNA--transthyretin (TTR), alpha1-anti-trypsin (AAT), alpha-fetoprotein (AFP), albumin (ALB), glucose-6-phoshpatase (G6P) and tyrosine aminotransferase (TAT). Approximately (85.1 +/- 0.5)% of the ES-derived cells was stained positive green with ICG uptake. These cells were also stained magenta as a result of PAS reaction. In this paper, expression of coagulation factors VIII and IX mRNA in the ES-derived cells is documented. Therefore, ES cells might be developed as substitute donor cells for the therapy of coagulation factor deficiencies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cell Differentiation
  • DNA Primers / genetics
  • Embryo, Mammalian / cytology*
  • Factor IX / genetics*
  • Factor VIII / genetics*
  • Gene Expression Profiling
  • Hemophilia A / therapy
  • Hemophilia B / therapy
  • Hepatocytes / cytology*
  • Hepatocytes / metabolism*
  • Humans
  • In Vitro Techniques
  • Mice
  • Pluripotent Stem Cells / cytology*
  • Pluripotent Stem Cells / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stem Cell Transplantation

Substances

  • DNA Primers
  • RNA, Messenger
  • Factor VIII
  • Factor IX