Liver stem-like (oval) cells: isolation, differentiation and application for cell therapy

We isolated oval cells from the liver of Long-Evans Cinnamon (LEC) rats by isopyknic centrifugation in a Percoll gradient. The cells were gamma-glutamyl transpeptidase positive, alpha-fetoprotein positive, cytokeratin 18 and 19 positive, but albumin negative in the cells. Among liver-enriched transcription factors, only HNF-3 beta mRNA was expressed, but HNF-3 alpha, HNF-4, HNF-1 alpha and C/EBP mRNAs were undetectable. When oval cells were transplanted to the liver, they were transformed into hepatocytes. To evaluate albumin biosynthesis, we transplanted oval cells into the liver of Nagase analbuminemic and LEC double mutant rats. The albumin level in the serum of transplanted rats was increased and maintained for up to 10 weeks. These results indicated that the oval cells isolated from LEC rats can differentiate into hepatocytes in vivo and can be used as a source for cell transplantation therapy to the liver.