DEMONSTRATION OF DIFFERENTIATION IN HEPATOCYTE PROGENITOR CELLS USINGDIPEPTIDYL PEPTIDASE-IV DEFICIENT MUTANT RATS

The presence of progenitor or stem cells in the adult liver and their potential roles in oncogenesis are unresolved issues. The study of hep atocyte progenitor cells has been limited by a lack of convenient in v ivo systems allowing unequivocal cell localization and demonstration o f differentiation into hepatocytes. To develop an in vivo progenitor b ioassay, early (E14) fetal Fischer 344 rat hepatoblasts were transplan ted into the spleen of syngeneic, weaning fats deficient in dipeptidyl peptidase IV (DPPIV) activity. The donor status of transplanted hepat oblasts was demonstrated by DPPIV expression. Localization of hepatobl asts was facilitated by the use of an ectopic site, as well as weanlin g recipients, which readily allowed identification of very small numbe rs of transplanted cells. Fetal rat hepatoblasts were demonstrated to undergo cellular differentiation along the hepatocyte lineage by acqui ring glucose-6-phosphatase activity within 5 d of transplantation. A c ritical review of previous transplantation studies of hepatocyte proge nitor cells and the role of the local microenvironment at inducing dif ferentiation indicates that this novel bioassay should facilitate anal ysis of progenitor cells.