Transdifferentiation of ductular cells into hepatocytes in regenerating hamster pancreas

The transdifferentiation of regenerating pancreatic cells into hepatocytes in the Syrian golden hamster and Fischer rat is an example of the surprising plasticity of cells in the adult animal. While earlier experiments suggested that these might be derived from acinar cells, unequivocal evidence of this in both models has not been forthcoming. In this paper, we document that pancreatic ductular epithelium in the hamster is the cell of origin and that presumptive hepatocytes can be identified morphologically as early as the 3rd day after the induction of regeneration. The patterns of development of various organelles as characterized by their acquisition of liver-specific protein markers parallels those that have been reported by others during the differentiation of embryonic and postnatal hepatocytes. Colloidal gold-labeled antibody staining of carbamoyl phosphate synthetase, a liver-specific mitochondrial enzyme, and catalase, a peroxisomal enzyme, first appeared 60 hours and 4.5 days postregeneration, respectively. At these times, the morphologic features of the hepatocyte phenotype in the pancreas were ambiguous. Morphometric analysis showed that for both enzymes, the number of gold particles/organelle increased to a maximum by the 9th week. In contrast, urate oxidase, a liver-specific peroxisomal enzyme, was not identified by ultrastructural immunochemistry until the 14th day after regeneration and remained at low levels through the 9th week.