Portosystemic shunting prevents hepatocellular carcinoma in non-alcoholic fatty liver disease mouse models.

Background And Aims: Non-alcoholic fatty liver disease (NAFLD) is one of the leading cause of hepatocellular carcinoma (HCC). This association is supported by the translocation of bacteria products into the portal system, which acts on the liver through the gut-liver axis. We hypothesize that portosystemic shunting can disrupt this relationship, and prevent NAFLD-associated HCC.

Anti-CD122 antibody restores specific CD8 T cell response in nonalcoholic steatohepatitis and prevents hepatocellular carcinoma growth.

Nonalcoholic steatohepatitis (NASH) can lead to hepatocellular carcinoma (HCC). Although immunotherapy is used as first-line treatment for advanced HCC, the impact of NASH on anticancer immunity is only partially characterized. We assessed the tumor-specific T cell immune response in the context of NASH.

FGF21 negatively affects long-term female fertility in mice.

Objective: Obesity and associated liver disease are a growing public health concern. Pharmacological agents to treat non-alcoholic fatty liver disease are limited. FGF21, a hormone secreted by the liver and potent metabolic modulator, is a promising therapeutic target for this indication with several analogs currently in clinical development.

Antibody-induced NKG2D blockade in a rat model of intraportal islet transplantation leads to a deleterious reaction.

Intraportal islet transplantation is plagued by an acute destruction of transplanted islets. Amongst the first responders, NK cells and macrophages harbour an activating receptor, NKG2D, recognizing ligands expressed by stressed cells. We aimed to determine whether islet NKG2D ligand expression increases with culture time, and to analyse the impact of antibody-induced NKG2D blockade in islet transplantation.

Tolerogenic properties of liver macrophages in non-alcoholic steatohepatitis.

Background & Aims: Our understanding of non-alcoholic fatty liver disease (NAFLD) pathogenesis is improving, but there is still limited data on the function of resident liver macrophages in this context, especially when considering their contribution in dampening liver inflammation.

Methods: Liver macrophages were studied in mouse models of prolonged diet-induced liver steatohepatitis and carbon tetrachloride-induced liver injury. We assessed liver macrophages phenotype and costimulatory/inhibitory properties upon exposure to lipopolysaccharide or interleukin 4.

The impact of short-term machine perfusion on the risk of cancer recurrence after rat liver transplantation with donors after circulatory death.

Hypothermic and normothermic ex vivo liver perfusions promote organ recovery after donation after circulatory death (DCD). We tested whether these perfusions can reduce the risk of hepatocellular carcinoma (HCC) recurrence in a 1h-DCD syngeneic transplantation model, using Fischer F344 rats. DCD grafts were machine perfused for 2h with hypothermic perfusion (HOPE) or normothermic perfusion (NORMO), and transplanted.

Effects of remote ischaemic preconditioning on intraportal islet transplantation in a rat model.

Remote ischaemic preconditioning (RIPC), which is the intermittent interruption of blood flow to a site distant from the target organ, is known to improve solid organ resistance to ischaemia-reperfusion injury. This procedure could be of interest in islet transplantation to mitigate hypoxia-related loss of islet mass after isolation and transplantation. Islets isolated from control or RIPC donors were analyzed for yield, metabolic activity, gene expression and high mobility group box-1 (HMGB1) content.

Chimeric liver transplantation reveals interspecific graft remodelling.

Background & Aims: A major limitation in the field of liver transplantation is the shortage of transplantable organs. Chimeric animals carrying human tissue have the potential to solve this problem. However, currently available chimeric organs retain a high level of xenogeneic cells, and the transplantation of impure organs needs to be tested.

Effects of the gut-liver axis on ischaemia-mediated hepatocellular carcinoma recurrence in the mouse liver.

Background & Aims: There is growing evidence that liver graft ischemia-reperfusion (I/R) is a risk factor for hepatocellular carcinoma (HCC) recurrence, but the mechanisms involved are unclear. Herein, we tested the hypothesis that mesenteric congestion resulting from portal blood flow interruption induces endotoxin-mediated Toll-like receptor 4 (Tlr4) engagement, resulting in elevated liver cancer burden. We also assessed the role of remote ischemic preconditioning (RIPC) in this context.

Dynamic Volume Assessment of Hepatocellular Carcinoma in Rat Livers Using a Clinical 3T MRI and Novel Segmentation.

Purpose: In vivo liver cancer research commonly uses rodent models. One of the limitations of such models is the lack of accurate and reproducible endpoints for a dynamic assessment of growing tumor nodules. The aim of this study was to validate a noninvasive, true volume segmentation method using two rat hepatocellular carcinoma (HCC) models, correlating magnetic resonance imaging (MRI) with histological volume measurement, and with blood levels of α-fetoprotein.

Impact of myeloid-derived suppressor cell on Kupffer cells from mouse livers with hepatocellular carcinoma.

Kupffer cells represent the first line of defense against tumor cells in the liver. Myeloid-derived suppressor cells (MDSC) have recently been observed in the liver parenchyma of tumor-bearing animals. The present study investigates the function of the MDSC subsets, and their impact on Kupffer cell phenotype and function.

Efficient nonarterialized mouse liver transplantation using 3-dimensional-printed instruments.

Because of the wide availability of genetically modified animals, mouse orthotopic liver transplantation is often preferred over rat liver transplantation. We present a simplified mouse liver transplantation technique and compare transplantation outcomes with versus without hepatic artery anastomosis. Instruments for liver implantation were designed and printed with a 3-dimensional (3D) printer.

Alloimmune Monitoring After Islet Transplantation: A Prospective Multicenter Assessment of 25 Recipients.

Islet transplantation is an effective treatment for selected patients with type 1 diabetes. However, an accurate test still lacks for the early detection of graft rejection. Blood samples were prospectively collected in four university centers (Geneva, Grenoble, Montpellier, and Strasbourg).

Pre-retrieval reperfusion decreases cancer recurrence after rat ischemic liver graft transplantation.

Background & Aims: Liver transplantation from marginal donors is associated with ischemia/reperfusion (I/R) lesions, which may increase the risk of post-transplant hepatocellular carcinoma (HCC) recurrence. Graft reperfusion prior to retrieval (as for extracorporeal membrane oxygenation--ECMO) can prevent I/R lesions. The impact of I/R on the risk of cancer recurrence was assessed on a syngeneic Fischer-rat liver transplantation model.

Alloimmune activation promotes anti-cancer cytotoxicity after rat liver transplantation.

Liver transplantation for hepatocellular carcinoma (HCC) results in a specific condition where the immune response is potentially directed against both allogeneic and cancer antigens. We have investigated the level of anti-cancer immunity during allogeneic immune response. Dark Agouti-to-Lewis and Lewis-to-Lewis rat liver transplantations were performed and the recipients anti-cancer immunity was analysed at the time of alloimmune activation.