Role of hepatic stellate cell/hepatocyte interaction and activation of hepatic stellate cells in the early phase of liver regeneration in the rat

Abstract

<h2>Abstract</h2><h3>Background/Aims</h3> Hepatic stellate cells (HSCs) are known to play a role in hepatic regeneration. We investigated hepatocyte/HSC interaction and HSC activation at various times after 70% partial hepatectomy (PHx) in the rat. <h3>Methods</h3> The hepatic microcirculation was studied using intravital fluorescence microscopy (IVFM). Desmin and α-SMA within liver tissue were detected by immunohistochemistry. In isolated parenchymal liver cells (PLCs) and HSCs, double immunostaining was used to identify activated HSC. <h3>Results</h3> Using IVFM, hepatocyte-clusters were often seen in vivo at 3 days after PHx (PHx3). Distance between HSC fell from 61.7±2.1 μm in controls to 36.1±1.4 μm (<i>P</i><0.001) while the HSC/hepatocyte ratio rose (0.71±0.01 to 1.08±0.03; <i>P</i><0.001). In >80% of in vivo microscopic fields in the PHx3 group, clusters of HSCs were observed especially near hepatocyte-clusters. At PHx1 and PHx3, >20% of cells in the PLC-fraction were HSCs which adhered to hepatocytes. At PHx3, in addition to desmin staining, isolated HSCs were also positive for BrdU and α-SMA, and formed clusters. HSCs in the HSC-fraction were only positive for desmin which indicated that adherence to hepatocytes is required for HSC activation. <h3>Conclusions</h3> Our data suggest that HSCs are activated by adhering to hepatocytes in the early phase of liver regeneration.