Crucial roles of mesodermal cell lineages in a murine embryonic stem cell-derived in vitro liver organogenesis system
| Autor: | Akihiro Suzuki, Shinichi Miyagawa, Akiko Kamiyoshi, Yasuhiko Hashikura, Jun Nakayama, Yoh-ichi Tagawa, Shinichiro Ogawa |
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| Jazyk: | angličtina |
| Rok vydání: | 2005 |
| Předmět: |
Time Factors
Liver cytology Cellular differentiation Blotting Western Angiogenesis Inhibitors Mice Transgenic Endothelial Growth Factors Embryoid body Biology Models Biological Peptides Cyclic Regenerative medicine law.invention Mesoderm Mice Ammonia law Culture Techniques Animals Cell Lineage Myocytes Cardiac Reverse Transcriptase Polymerase Chain Reaction Stem Cells Temperature Bioartificial liver device Cell Biology Embryo Mammalian Immunohistochemistry Liver Artificial Embryonic stem cell Thalidomide Cell biology Platelet Endothelial Cell Adhesion Molecule-1 Endothelial stem cell Liver Immunology Hepatocytes Hepatic stellate cell RNA Molecular Medicine Developmental Biology |
| Zdroj: | Stem Cells. 23(No. 7):903-913 |
| Popis: | Recent studies in the field of regenerative medicine have exploited the pluripotency of embryonic stem (ES) cells to generate a variety of cell lineages. However, the target has always been only a single lineage, which was isolated from other differentiated cell populations. In the present study, we selected sublines with a high capability for differentiation to contracting cardiomyocytes and also produced germ-line chimeric mice from a parent ES line. We also succeed in establishing embryoid bodies prepared from the ES cells that differentiated into not only hepatocytes but also at least two mesodermal lineages: cardiomyocytes that supported liver development and endothelial cells corresponding to sinusoids. This allowed the development of an in vitro system using murine ES cells that approximated the events of liver development in vivo. The expression of albumin was significantly higher in cardiomyocytes that had arisen in differentiated ES cells than in those that had not. Our in vitro system for liver organogenesis consists of a blood/sinusoid vascular-like network and hepatocyte layers and shows higher levels of hepatic function, such as albumin production and ammonia degradation, than hepatic cell lines and primary cultures of murine adult hepatocytes. This innovative system will lead to the development of second-generation regenerative medicine techniques using ES cells and is expected to be useful for the development of bioartificial liver systems and drug-metabolism assays. |
| Databáze: | OpenAIRE |
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