2B). Whereas hepatocytes in cirrhosis had a wider rate of proliferation than those in normal liver, the difference did not reach statistical significance in

this study. p21 and PCNA labeling indices showed no significant difference between EpCAM(+) hepatocytes and EpCAM(−) hepatocytes (Fig. 3). The telomere lengths were measured by studying from 50 to 214 telomere dots www.selleckchem.com/products/apo866-fk866.html (telomere length signal detected by quantitative fluorescence in situ hybridization) according to cell type in nine cases of normal liver (Fig. 4G; Supporting Table 3). In normal liver, there was no significant difference in telomere lengths among normal hepatocytes, canal of Hering cells and bile duct cells (Fig. 5A), nor did they differ according to age or sex. In selleck cirrhotic livers, the telomere lengths were measured by studying from 33 to 189 telomere dots according to cell type in six cases (Fig. 4G; Supporting Table 4). When comparing

the telomere lengths between EpCAM(+) hepatocytes and EpCAM(−) hepatocytes in cirrhosis, the telomere lengths of EpCAM(−) hepatocytes were significantly shorter than those of EpCAM(+) hepatocytes (P = 0.046). In addition, EpCAM(+) hepatocytes showed relatively shorter telomere length than ductular reactions (P = 0.057), whereas EpCAM(−) hepatocytes showed significantly shorter telomere length than ductular reactions (P = 0.016) (Figs. 4 and 5A). There was no significant difference in telomere length according to patient age in both cirrhotic and normal livers. When the telomere lengths of ductular reactions, EpCAM(+) hepatocytes, and EpCAM(−) hepatocytes were traced in each patient, there was gradual telomere shortening from ductular reaction to EpCAM(+) hepatocytes and to EpCAM(−) hepatocytes (Fig. 5B). A growing body of work in the last few decades has identified cells of the ductular reactions in human livers in diverse but usually severe

acute and chronic liver diseases as being the equivalent of the oval cells seen in rodent models of injury.1, 2, 5, 11-16, 18 As such, the ductular reactions are thought to be the transit amplifying cells deriving from activation of the stem cell compartments of the liver.1, 7 Like oval cells, the 上海皓元医药股份有限公司 cells are thus thought to have at least two possible differentiation pathways, toward hepatocytes and toward cholangiocytes, the dominant direction being determined by the presence of injury and the nature and severity of that injury. In diseases with a predominance of hepatocyte injury, the ductular reaction is triggered by acute destruction of large amounts of parenchyma11 or by senescence of hepatocytes by chronic low level injury, and presumably results in hepatocyte replenishment from the stem/progenitor cell compartments.