Trophism and Homeostasis of Liver Sinusoidal Endothelial Graft Cells during Preservation, with and without Hypothermic Oxygenated Perfusion

Abstract

The aim of the present study was to evaluate the homeostasis and trophism of liver sinusoidal endothelial cells (LSECs) in vivo in different stages of liver graft donation, in order to understand the effects of graft ischemia and perfusion on LSEC activity in liver grafts. Special attention was paid to grafts that underwent hypothermic oxygenated perfusion (HOPE). Forty-seven donors were prospectively enrolled, and two distinct biopsies were performed in each case: one allocation biopsy (at the stage of organ allocation) and one post-perfusion biopsy, performed after graft implant in the recipients. In all biopsies, immunohistochemistry and RT-PCR analyses were carried out for the endothelial markers CD34, ERG, Nestin, and VEGFR-2. We observed an increase in CD34 immunoreactivity in LSEC during the whole preservation/perfusion period (p < 0.001). Nestin and ERG expression was low in allocation biopsies, but increased in post-perfusion biopsies, in both immunohistochemistry and RT-PCR (p < 0.001). An inverse correlation was observed between ERG positivity and donor age. Our results indicate that LSEC trophism is severely depressed in liver grafts, but it is restored after reperfusion in standard conditions. The execution of HOPE seems to improve this recovery, confirming the effectiveness of this machine perfusion technique in restoring endothelial functions.

Association between Hepatocellular Carcinoma Recurrence and Graft Size in Living Donor Liver Transplantation: A Systematic Review

“…Based on the underlying mechanism of protection, this perfusion technique reduces posttransplant complications, improves graft survival and reduces re-transplantation rates [ 76 , 82 ]. The concept of improved peripheral sinusoidal flow and microvascular protection through the HOPE concept is also interesting [ 83 , 84 ]. In the context of LDLT, existing experimental studies demonstrated an improved growth and earlier entrance into the cell-cycle for quicker liver regeneration after hypothermic perfusion [ 85 , 86 , 87 ].…”

Endothelial Cells and Mitochondria: Two Key Players in Liver Transplantation

“…Six studies used an animal model (either porcine or rodent), and one tested such effects in discarded human livers. Tissue samples from two clinical transplant studies were assessed for EC protection with HOPE and correlated with posttransplant outcomes [ 75 , 76 ]. One study combined rodent experiments with human liver transplants in a model of severe macrosteatosis [ 77 ].…”

“…Tissue samples from this study were assessed for EC integrity and activation. Vasuri et al analyzed 47 human livers from a randomized controlled trial (RCT) in Italy transplanting ECD livers with HOPE or cold storage [ 60 , 75 ]. The authors describe endothelial trophism and intracellular homeostasis measured through Nestin expression after HOPE.…”

“…The authors describe endothelial trophism and intracellular homeostasis measured through Nestin expression after HOPE. Additionally, liver SEC endothelization is an interesting parameter useful to assess the response to elevated portal pressures that can show a metaplastic EC shift to a cell subtype with reduced specialization being protected from high portal pressure [ 75 ].…”

Translational Aspects of Cardiovascular Biology: From Bench to Bedside

“…The second study provides a demonstration of the extracellular metabolism of nicotinamide adenine dinucleotide (NAD+) and nicotinamide mononucleotide (NMN), multifunctional metabolites involved in a number of cellular processes, and which is vastly different in its expression in the vascular endothelium obtained from different species and locations [2]. The third paper, instead, deals with the functions and intracellular mechanisms of endothelial cells in human liver grafts [3].…”