Authors: Budny, Tymoteusz¹; Palmes, Daniel¹; Stratmann, Udo²; Minin, Evgeny³; Herbst, Hermann³; Spiegel, Hans-Ullrich⁴

Source: Virchows Archiv, Volume 451, Number 4, October 2007 , pp. 781-791(11)

Publisher: Springer

Abstract:

Different cell types play a role in the liver regeneration. The present study reveals morphological key steps of liver regeneration by correlating intravital, light, and electron microscopic with immunohistochemistry results focusing on hepatic stellate cells (HSCs). In Lewis rats, liver regeneration was induced by a 2/3-hepatectomy. Animals (n = 7 each) were killed after 0, 1, 2, 3, 4, 7, and 14 days. Morphological features were investigated by light microscopy, immunohistochemistry [α-smooth muscle actin (α-SMA), Desmin, vascular endothelial growth factor (VEGF)/VEGF receptor, Ki-67, ssDNA], intravital microscopy (sinusoid density, number of hepatocytes, and HSC), and electron microscopy focussed on cell-to-cell interactions. During liver regeneration, HSC were activated at day 3 showing a loss of autofluorescence and simultaneously an increased α-SMA expression and direct cell contact to hepatocytes. HSC activation was followed by increasing VEGF expression and sinusoid density. After 14 days, liver architecture and ultrastructure was restored and HSCs were deactivated showing decreased α-SMA expression as well as increased apoptosis and no more direct cell contact to hepatocytes. HSCs play a central role in the regenerating liver by governing angiogenesis and extracellular matrix remodeling. A direct cell contact to hepatocytes seems to be essential for HSC activation, whereas deactivation is accompanied by loosening of hepatocyte contact and increased apoptosis.

Keywords: Liver regeneration; Hepatic stellate cells; Angiogenesis; Electron microscopy; Intravital microscopy; Light microscopy

Document Type: Research article

DOI: http://dx.doi.org/10.1007/s00428-007-0472-x

Affiliations: 1: Surgical Research, Department of General Surgery, Muenster University Hospital, Waldeyer Str. 1, 48149, Muenster, Germany 2: Institute of Anatomy, Muenster University Hospital, Muenster, Germany 3: Gerhard-Domagk-Institute of Pathology, Muenster University Hospital, Muenster, Germany 4: Surgical Research, Department of General Surgery, Muenster University Hospital, Waldeyer Str. 1, 48149, Muenster, Germany, Email: spiegeh@uni-muenster.de

Publication date: 2007-10-01

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