Liver Regeneration and New Technical Possibilities by Two-photon Based Intravital Imaging

Abstract

One of the outstanding features of the liver is its enormous regeneration capacity. Compared to other solid organs, such as kidney, pancreas, heart or brain, the liver shows a superior capacity to regenerate. Probably, this regeneration capacity has evolved during ‘animal plant warfare’, when plants protected themselves from herbivores by new toxins and herbivores responded by novel detoxifying enzymes and efficient hepatic regeneration. Control mechanisms of liver regeneration have attracted scientists since decades. One limitation that has hampered progress is the lack of possibilities or real-time observations of cellular and subcellular processes in the regenerating liver without removing the organ for analysis. This has now become possible by the introduction of an improved technology of two-photon based intravital imaging. This technology allows the possibility to perform real-time imaging of the intact liver in anesthetized mice. Resolution is close to the theoretically possible 200 nm and therefore allows imaging of organelles and vesicles. Also, imaging of fast processes in the millisecond range is possible. Using available fluorescent reporter mouse systems it is possible to visualize all resident cell types of the liver, such as hepatocytes, Kupffer cells, stellate cells and sinusoidal endothelial cells. Furthermore, infiltrating immune cells can be imaged during liver injury and regeneration using cell-specific antibodies or reporter mice. This minireview presents some of the possibilities of intravital imaging and its applicability for research in the field of liver regeneration.