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(American Journal of Pathology. 2001;158:97-105.)
© 2001 American Society for Investigative Pathology

Regular Articles

Size-Dependent in Vivo Growth Potential of Adult Rat Hepatocytes

Shigeru Katayama*{dagger}, Chise Tateno*, Toshimasa Asahara{dagger} and Katsutoshi Yoshizato*{ddagger}

From the Hiroshima Tissue Regeneration Project,*
Hiroshima Prefecture Joint-Research Project for Regional Intensive, Japan Science and Technology Corporation, Hiroshima Prefectural Institute of Industrial Science and Technology, Higashihiroshima; the Department of Second Surgery,{dagger}
School of Medicine, Hiroshima University, Higashihiroshima; and the Developmental Biology Laboratory,{ddagger}
Department of Biological Science, Graduate School of Science, Hiroshima University, Higashihiroshima, Hiroshima, Japan

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.




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