Size-dependent in vivo growth potential of adult rat hepatocytes

The present study was performed to determine whether hepatocytes show a size-dependent growth in vivo using as a growth assay system, a retrorsine/partial hepatectomy model of dipeptidyl dipeptidase IV-deficient (DPPIV(-)) mutant Fischer rats. Nearly pure populations of small hepatocytes (SHs) and parenchymal hepatocytes (PHs) were prepared from DPPIV(+) rats. The same number of these SHs and PHs was transplanted into the liver of retrorsine-treated and two-thirds partial hepatectomized DPPIV(-) rats. At 21 days after transplantation, colonies derived from donor hepatocytes were detected as DPPIV(+) cells by enzyme histochemistry. SHs were approximately three times more proliferative than PHs (673 +/- 25 cells/colony versus 226 +/- 10 cells/colony, mean +/- SE). SHs were subfractionated by a fluorescence-activated cell sorter into SH-R2s and SH-R3s. SH-R3s showed a lower extent of granularity and autofluorescence, and a smaller size than SH-R2s that showed characteristics similar to PHs. The growth potential of SH-R3s assayed as above was approximately three times higher than that of SH-R2s (1,101 +/- 46 cells/colony versus 341 +/- 13 cells). These results indicate that the in vivo growth potential of hepatocytes is heterogeneous and is correlated with their size, and the extent of their granularity and autofluorescence.