RRC ID |
1438
|
著者 |
Ogawa S, Tagawa Y, Kamiyoshi A, Suzuki A, Nakayama J, Hashikura Y, Miyagawa S.
|
タイトル |
Crucial roles of mesodermal cell lineages in a murine embryonic stem cell-derived in vitro liver organogenesis system.
|
ジャーナル |
Stem Cells
|
Abstract |
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.
|
巻・号 |
23(7)
|
ページ |
903-13
|
公開日 |
2005-8-1
|
DOI |
10.1634/stemcells.2004-0295
|
PII |
23/7/903
|
PMID |
16043458
|
MeSH |
Ammonia / pharmacology
Angiogenesis Inhibitors / pharmacology
Animals
Blotting, Western
Cell Lineage*
Culture Techniques*
Embryo, Mammalian / cytology*
Endothelial Growth Factors / pharmacology
Hepatocytes / cytology
Hepatocytes / metabolism
Immunohistochemistry
Liver / cytology*
Liver / metabolism
Liver, Artificial
Mesoderm / cytology*
Mice
Mice, Transgenic
Models, Biological
Myocytes, Cardiac / cytology
Peptides, Cyclic / pharmacology
Platelet Endothelial Cell Adhesion Molecule-1 / biosynthesis
RNA / metabolism
Reverse Transcriptase Polymerase Chain Reaction
Stem Cells / cytology*
Temperature
Thalidomide / pharmacology
Time Factors
|
IF |
6.022
|
引用数 |
48
|
WOS 分野
|
BIOTECHNOLOGY & APPLIED MICROBIOLOGY
HEMATOLOGY
ONCOLOGY
CELL BIOLOGY
CELL & TISSUE ENGINEERING
|
リソース情報 |
ヒト・動物細胞 |
STO(RCB0536) |