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

• Published in: Science in China. Series C, Life sciences Life sciences, 2006-06, Vol.49 (3), p.259-264
• Main Authors: Meng, Ying, Huang, Shaoliang, Min, Jun, Guo, Zhongmin
• Format: Article
• Language: English
• Subjects: 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; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; RNA, Messenger - metabolism; Stem Cell Transplantation
• ISSN: 1006-9305; 1862-2798
• DOI: 10.1007/s11427-006-0259-3

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.