Endogenous and Transplanted Small Hepatocytes in Retrorsine-treated/Partially Hepatectomized Rat Liver Show Differences in Growth, Phenotype, and Proximity to Clusters of γ-Glutamyl Transpeptidase-positive Host Hepatocytes

In the present report, we have compared the phenotype and growth of small hepatocyte progenitors (SHPs) induced by retrorsine/partial hepatectomy (R/PH) and small hepatocytes (SHs) isolated from normal adult liver. SHs were isolated by a combination of differential centrifugation and Percoll isodensity fractionation from a liver cell suspension prepared by collagenase perfusion of a dipeptidyl peptidase IV (DPPIV)-positive Fischer F344 rat liver. Following further purification by flow cytometry, the SH-R3 fraction was transplanted via the portal vein into R/PH-treated, DPPIV-negative Fischer F344 rats. Frozen sections from tissue harvested at 5, 7, and 21 days after transplantation were analyzed by indirect immunofluorescence to compare the phenotypic characteristics of colonies formed by exogenous SH-R3s and endogenous SHPs. Colonies of transplanted SHs and endogenous SHPs displayed similar histologies and phenotypes but were distinguished from surrounding hepatocytes by their elevated expression of transferrin receptor. SH-R3 colonies were frequently located within clusters of γ-glutamyl transpeptidase-positive host hepatocytes. Although significantly smaller at 5 and 7 days after PH, by day 21, SH-R3 colonies were similar in size to those formed by SHPs. The present results suggest that endogenous SHPs are derived, at least in part, from SHPs.