Differentiation of embryonic stem cells into hepatocytes: biological functions and therapeutic application.
Embryonic stem (ES) cells provide a unique source for tissue regeneration. We examined whether mouse ES cells can efficiently differentiate into transplantable hepatocytes. ES cells were implanted into mouse livers 24 hours after carbon tetrachloride intoxication; ES-derived cells with several hepatocyte-cell-markers were generated. They were able to grow in vitro and showed morphology consistent with typical mature hepatocytes and expressed hepatocyte-specific genes. After transplantation into the carbon tetrachloride-injured mouse liver, ES-derived green fluorescent protein-positive cells were incorporated into liver tissue and rescued mice from hepatic injury. No teratoma formation was observed in the transplant recipients. In conclusion, ES cells can provide a valuable tool for studying the molecular basis for differentiation of hepatocytes and form the basis for cell therapies.
Yamamoto
Hanako
H
National Cancer Center Research Institute, Tokyo, Japan.
Quinn
Gary
G
Asari
Akira
A
Yamanokuchi
Hiroko
H
Teratani
Takumi
T
Terada
Masaaki
M
Ochiya
Takahiro
T
D000418:Albumins / Q000235:genetics; D000818:Animals; D002251:Carbon Tetrachloride; D002454:Cell Differentiation; D002478:Cells, Cultured; D056486:Chemical and Drug Induced Liver Injury / Q000628:therapy*; D005260:Female; D049452:Green Fluorescent Proteins; D022781:Hepatocytes / Q000166:cytology* / Q000378:metabolism; D007150:Immunohistochemistry; D007202:Indicators and Reagents / Q000378:metabolism; D008115:Liver Regeneration; D008164:Luminescent Proteins / Q000235:genetics; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology*
D000418:Albumins; D007202:Indicators and Reagents; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins; D002251:Carbon Tetrachloride