Establishment of cell transplantation therapy for Wilson's disease using hepatic stem cells.

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[Aim]In this study, we aimed the establishment of cell transplantation therapy for metabolic liver diseases using hepatic stem cells, previously isolated from a rat liver. To this end, we examined function of the transplanted hepatic stem cells into liver whether cell transplantation was effective to treat metabolic liver diseases including Wilson's disease.[Achievements](1) We have established a liver epithelia cell line, designated hepatic stem like (HSL) cell, from nonparenchymal fraction of healthy rat liver. (2) The HSL cells are small with 20μm in diameter and showed high nucleus/cytoplasm ratios. These cells expressed α-fetoprotein, but not albumin nor cytokeratin 19, indicating the cells have immature phenotype. (3) We cultured the HSL cells in collagen gels cr with hepatic stellate cells to investigate their potential to differentiate. Consequently, both of culture conditions induced the HSL cells to express albumin, showing that the HSL cells are able to differentiate into mature cells. (4) Finally, we examined whether the HSL cells will be able to manifest hepatic function in vivo after transplantation. To this end, we transplanted the HSL cells that were mixed with collagen gel or embedded in collagen sponge into analbuminemic rats. As a result, analbuminemic rats that showed the increased levels of serum albumin were 67% in the rats transplanted the HSL cells with collagen gel and 57% in the rats with collagen sponge. In those rats, the levels of serum albumin increased ten weeks after transplantation and maintained until 25 weeks after transplantation. These results suggest that the HSL cells are potential to differentiate and that the transplanted HSL cells differentiated into albumin producing cells and function as hepatocytes in vivo. The present study implies the possibility of clinical application of HSL cells for metabolic liver diseases.