Critical Role of LSEC in Post-Hepatectomy Liver Regeneration and Failure

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.

Spatiotemporal expression of HMGB2 regulates cell proliferation and hepatocyte size during liver regeneration

“…In WT mouse livers, the spatiotemporal expression of HMGB2 was strongly correlated with active cell proliferation, especially at 36–72 h after PHx. Our results also confirmed that hepatocytes are the first dividing cells, followed by proliferation of cholangiocytes and endothelial cells 21 , 22 . The expression of Ki-67 is a reliable marker of dividing cells, and it is not expressed in G 0 phase 23 .…”

Expression, Prognostic Value, and Functional Mechanism of Polarity-Related Genes in Hepatocellular Carcinoma

“…This could be indirect evidence for possible expansion of those existing drug markets. However, hepatocytes behave quite differently in terms of polarity characteristics in the traditional in vitro 2D culture condition [ 39 , 40 ]. An in vitro collagen sandwich system sheds light on the dilemma, in which primary hepatocytes are isolated and cultured inside two layers of collagen, showing the exciting ability to re-establish cell polarity and maintain hepatic functions [ 41 ].…”

The role of platelet mediated thromboinflammation in acute liver injury

“…LSECs produce mitotic substances, specifically IL-6, hepatocyte growth factor and VEGF ( 152 ). Direct adhesion between platelets and LSECs induces IL-6 release, in turn, leading to hepatocyte growth factor secretion from hepatic stellate cells promoting hepatocyte regeneration in vitro ( 153 ).…”