Quantification of hepatic vascular regeneration after 70% partial hepatectomy in mice : tools and application

Liver regeneration consists of parenchymal regeneration and vascular growth. Due to technical limitation in quantifying vascular regeneration, more efforts were spent on studying parenchymal regeneration rather than vascular regeneration. However, vascular is crucial in liver regeneration. Thus, this study aims for improving techniques for quantifying hepatic vascular regeneration in mice. First, we established a delicate monitoring procedure suitable for mice for acquiring hepatic hemodynamic parameters. Portal blood flow and portal venous pressure were measured in normal and resected mice. Second, we adapted the silicone injection method for visualizing and quantifying the changes of vascular regenerative parameters after resection in mice. Maximal vessel length and in/outflow radius of right inferior portal vein were measured. Cumulative vascular regenerative parameters were calculated based on the vascular geometry. Moreover, the underlying growth pattern was explored. Forth, we applied the established work flow to visualize and quantify the vascular growth after modulating the CXCR4 signaling pathway by blocking CXCR4 and/or activating CXCR7. Despite the seemingly homogeneous 3D-growth, the observed vascular parameters were not compatible with the hypothesis of isotropic expansion of liver parenchyma and vascular structures. Liver regeneration was not affected by only blocking CXCR4 but was impaired after blocking CXCR4 in the meanwhile activating CXCR7, pointing to the relevance of this pathway for liver regeneration. In conclusion, we explored vascular liver regeneration in a meso- and macroscopic scale. Altogether, this study provides technical tools to further and deeper explore and understand hepatic vascular regeneration after liver resection.