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

Abstract

S U M M A R YIn 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 g-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. (J Histochem Cytochem 58:61-72, 2010)

Changes in the proteome of extracellular vesicles shed by rat liver after subtoxic exposure to acetaminophen

“…Their goal was to evaluate early changes in hepatic‐derived exosomes that occur during liver stress caused by subtoxic dosage of APAP and rats were selected as a relatively resistant preclinical species. Support for the discussed arguments was acquired in the framework of a well‐established and researched rat model [38,39,41].…”

“…Treated and control animals were euthanized 12 h after APAP administration. Euthanasia was performed using CO 2 inhalation followed by cervical dislocation [39,40].…”

“…Their goal was to evaluate early changes in hepatic-derived exosomes that occur during liver stress caused by subtoxic dosage of APAP and rats were selected as a relatively resistant preclinical species. Support for the discussed arguments was acquired in the framework of a well-established and researched rat model [38,39,41]. Most investigations of mouse or rat liver EVs have been performed with EV isolated from blood plasma collected from experimental animals or isolated from cultured hepatocytes [1,18,30].…”

“…Guidelines for the standardization of the isolated perfused rat liver (IPRL), according to Tateno et al and Bassems et al[39,40], with permission…”

An Optimal Medium Supplementation Regimen for Initiation of Hepatocyte Differentiation in Human Induced Pluripotent Stem Cells

“…The 201B7 cells expressed AFP and γ‐GTP. The former is a marker of immature hepatocytes and the latter, of bile duct epithelial cells [Tateno et al, ; Inamura et al, ]. These results suggested that the cells were hepatoblast‐like cells because they had characters of both immature hepatocytes and bile duct epithelial cells [Tomizawa et al, ].…”