Reversal of mouse hepatic failure using an implanted liver-assist device containing ES cell-derived hepatocytes.

Severe acute liver failure, even when transient, must be treated by transplantation and lifelong immune suppression. Treatment could be improved by bioartificial liver (BAL) support, but this approach is hindered by a shortage of human hepatocytes. To generate an alternative source of cells for BAL support, we differentiated mouse embryonic stem (ES) cells into hepatocytes by coculture with a combination of human liver nonparenchymal cell lines and fibroblast growth factor-2, human activin-A and hepatocyte growth factor. Functional hepatocytes were isolated using albumin promoter-based cell sorting. ES cell-derived hepatocytes expressed liver-specific genes, secreted albumin and metabolized ammonia, lidocaine and diazepam. Treatment of 90% hepatectomized mice with a subcutaneously implanted BAL seeded with ES cell-derived hepatocytes or primary hepatocytes improved liver function and prolonged survival, whereas treatment with a BAL seeded with control cells did not. After functioning in the BAL, ES cell-derived hepatocytes developed characteristics nearly identical to those of primary hepatocytes.

Formation of dentin-like particles in dentin defects above exposed pulp by controlled release of fibroblast growth factor 2 from gelatin hydrogels.

The induction of dentin formation on exposed dental pulp is a major challenge in research on the regeneration of the dentin-pulp complex. We examined the effects of fibroblast growth factor 2 (FGF2), which was delivered in either a collagen sponge (noncontrolled release) or incorporated into gelatin hydrogels (controlled release), on the formation of dentin in exposed rat molar pulps. During the early phase of pulp wound healing, pulp cell proliferation and invasion of vessels into dentin defects above exposed pulp were induced in both groups. In the late phase, the induction of dentin formation was distinctly different between the 2 types of FGF2 release. The noncontrolled release of free FGF2 from collagen sponge induced excessive reparative dentin formation in the residual dental pulp, although dentin defects were not noted. In contrast, controlled release of FGF2 from gelatin hydrogels induced the formation of dentin-like particles with dentin defects above exposed pulp. These results suggest the possibility of a novel therapeutic approach for dentin-pulp complex by controlled release of bioactive FGF2.