Development of efficient process for isolation, propagation and differentiation induction of normal human hepatic stem cells and its application to artificial liver

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1, Studies on transformation of normal human hepatic stem cells in propagation process and its preventionIf the normal human hepatic stem cells (hepatoblast) transform in propagation process, these cells can not be applicable to regenerative medicine and artificial liver. In fact, the stem cells and transformed tumor cells have similar characteristics and makers. In this research, we developed the examination method for the transformation of hepatic stem cells (hepatoblast) using PIVKA-II (abnormal prothrombin) as a maker, which is clinical tumor maker of hepatocytes. We indicated that human fetal hepatocytes including hepatoblasts started to transform at the8th passage of propagation by using PIVKA-II assay. And we also indicated that induction of hepatoblast from human fetal hepatocytes teated with Sodium butyrate, caused the transformation depended on the concentration of sodium butyrate. It was also found that Vitamin K has prevention effect of the transformation of human fetal heptaocytes.2,Studies on the materials of culture substrate for high density culture of hepatoblast.For development of artificial liver module using human hepatoblast, it is necessary to study on material characteristics of culture substrate for high density culture, functional expression and prevention of transformation of human hepatoblast. In this research, we examined several culture substrates. Macroporous siran material was better for high density culture. And porous hydroxyapatite was better for cytochrome P450 activity expression of hepatoblast.