Differentiation of Embryonic Stem Cells Into Hepatocytes: Biological Functions and Therapeutic Application

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Abstract
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.