Abstract
Liver sinusoids are lined by liver sinusoidal endothelial cells (LSEC), which represent approximately 15 to 20% of the liver cells, but only 3% of the total liver volume. LSEC have unique functions, such as fluid filtration, blood vessel tone modulation, blood clotting, inflammatory cell recruitment, and metabolite and hormone trafficking. Different subtypes of liver endothelial cells are also known to control liver zonation and hepatocyte function. Here, we have reviewed the origin of LSEC, the different subtypes identified in the liver, as well as their renewal during homeostasis. The liver has the exceptional ability to regenerate from small remnants. The past decades have seen increasing awareness in the role of non-parenchymal cells in liver regeneration despite not being the most represented population. While a lot of knowledge has emerged, clarification is needed regarding the role of LSEC in sensing shear stress and on their participation in the inductive phase of regeneration by priming the hepatocytes and delivering mitogenic factors. It is also unclear if bone marrow-derived LSEC participate in the proliferative phase of liver regeneration. Similarly, data are scarce as to LSEC having a role in the termination phase of the regeneration process. Here, we review what is known about the interaction between LSEC and other liver cells during the different phases of liver regeneration. We next explain extended hepatectomy and small liver transplantation, which lead to “small for size syndrome” (SFSS), a lethal liver failure. SFSS is linked to endothelial denudation, necrosis, and lobular disturbance. Using the knowledge learned from partial hepatectomy studies on LSEC, we expose several techniques that are, or could be, used to avoid the “small for size syndrome” after extended hepatectomy or small liver transplantation.
Highlights
liver sinusoidal endothelial cells (LSEC) Are “Liver-Specialized” Endothelial CellsEndothelial cells (EC) form the barrier between blood and tissue, and control the flow of fluid, substances and cells into and out of a tissue
Academic Editor: Laboratory of Hepato-Gastroenterology, Institute of Experimental and Clinical Research, UCLouvain, HPB Surgery Unit, Centre Hospitalier Universitaire UCL Namur, Site Mont-Godinne, 5530 Yvoir, Belgium
We presented research supporting the critical role of liver sinusoidal endothelial cells (LSEC) during liver regeneration
Summary
Endothelial cells (EC) form the barrier between blood and tissue, and control the flow of fluid, substances and cells into and out of a tissue. Unlike in larger vessels where the endothelium is held by a basement membrane, the endothelial cells of the liver sinusoids lie on a lose extracellular matrix of the space of Disse and are fenestrated They form a highly permeable capillary [11], enabling an easy bidirectional traffic of macromolecules and diverse metabolites from blood to the hepatocytes, and vice versa. Capillarization, describing the loss of fenestration and densification of the basal extracellular matrix, is a common phenomenon occurring in chronic liver disease during fibrogenesis or with aging that impedes blood-hepatocytes molecular exchanges and contributes to reduce hepatocellular function It is not known whether capillarization is a cause or a consequence of chronic liver disease, capillarized LSEC participate in the activation of hepatic stellate cells, further worsening fibrosis [12,13]
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