Prior ligation of portal branches improves survival after a 90% portal hepatectomy in the rat

The ligation of portal branches is known to induce an atrophy of the deprived lobes and a hypertrophy of the nonligated lobes. In this work, we examined if this response occurs when the ligation affects 90% of the liver mass and if it is able to influence the survival rate after a hepatectomy of this magnitude. In male Wistar rats, major portal branches were ligated, keeping open only a small branch supplying the papillary lobes. The ligated lobes underwent a progressive weight loss and their DNA synthesis remained at the level of the controls. The nonligated lobes started to gain weight on the first postoperative day and had increased about 5-fold by the 14th day. The DNA synthesis in these lobes was greatly enhanced with a peak increase at 24 h. Two weeks after a similar ligation of portal branches, the ligated lobes, representing initially 90% of the liver mass, were resected and 80% of the rats survived. In the control group submitted only to a sham operation 2 weeks before, all rats died within 48 h after resection of the corresponding lobes. These results demonstrate that ligation of portal branches feeding 90% of the liver mass can be well tolerated and induces an atrophy of the ligated lobes and a hypertrophy of the nonligated lobes. This procedure, which improves the survival rate after an extended hepatectomy performed 2 weeks later, could find some clinical application

Although pig allogeneic mesenchymal stem cells are not immunogenic in vitro, intracardiac injection elicits an immune response in vivo.

BACKGROUND: In vitro, mesenchymal stem cells (MSCs) have demonstrated a low immunogenic profile. In this study, we tested the immune response to allogeneic MSCs in immunocompetent swines both in vitro and in vivo. METHODS: Major histocompatibility complex-controlled swine leukocyte antigen (SLA) and SLA were used as donor and recipient, respectively. In vitro, proliferative responses were tested by mixed lymphocyte reaction (MLR) or cocultures and cytokine profiling by enzyme-linked immunosorbent assay. In vivo, allogeneic MSCs were injected in cardiac infarcted area (n=3) and compared with subcutaneous injections of either MSCs (n=2) or peripheral blood mononuclear cells (PBMCs; n=2). Two additional animals received a skin graft as controls. No immunosuppression was used. Specific antidonor humoral responses were tested by flow cytometry and complement-dependent cytotoxicity assay. RESULTS: In vitro, either unstimulated MSCs or interferon (IFN)-gamma stimulated MSC failed to elicit a proliferative response (stimulation index: 1.23 vs. 1.12 vs. 36.9 for controls, P<.001). Concomitantly to the absence of proliferation to MSCs, low production of IFN-gamma and interleukin-2 was evidenced in supernatants while the production of Th2 cytokines was comparable to controls. In vivo, all animals receiving skin grafts, subcutaneous PBMCs and intracardiac MSCs injections developed donor-specific cellular and humoral responses (immunoglobulins M and G) with antibody-complement-mediated cytotoxicity. Subcutaneous MSCs injection needed a rechallenge to similarly develop a cytotoxic humoral response. CONCLUSIONS: Intracardiac allogeneic porcine mesenchymal stem cells elicit an immune response despite their low immunogenic profile in vitro. This result suggests that in vivo characteristics of allogeneic MSCs might differ and emphasizes the importance of pursuing research both in vitro and in vivo

Kupffer Cell Depletion and the Intensity of the Proliferative Response After a 1/3 Or a 2/3 Partial-hepatectomy

Kupffer Cell Depletion and the Intensity of the Proliferative Response After a 1/3 Or a 2/3 Partial-hepatectom

Interaction of Hepatocyte Growth-factor With Changes Produced in the Liver After Partial-hepatectomy

Interaction of Hepatocyte Growth-factor With Changes Produced in the Liver After Partial-hepatectom

Inhibition of the Ras oncoprotein reduces proliferation of hepatocytes in vitro and in vivo in rats.

Ras oncoproteins are probably implicated in normal and malignant cell growth in various organs. Inhibition of Ras interferes with cell proliferation of non-hepatic cells in vitro and in vivo. A potential role for Ras in normal and malignant hepatocyte proliferation prompted us to evaluate the impact of Ras inhibition by FTS (S-farnesylthiosalicylic acid) on hepatocyte proliferation in vitro in the human hepatic tumour cell line HepG2 and in vivo after PH (partial hepatectomy) in rats. Rats were administered with FTS intraperitoneally (1, 8 and 16 h after PH) and killed 12, 24 and 48 h after PH. Cell proliferation, phosphorlyation of members of the MAPK (mitogen-activated protein kinase) pathway and levels and activity of cell cycle effectors (cyclin D, cyclin E, Cdk2 and Cdk4) were assessed in FTS-treated rats compared with controls. FTS significantly decreased overall cell count, PCNA (proliferating-cell nuclear antigen) expression and BrdU (bromodeoxyuridine) incorporation into HepG2 cells after 7 days of culture. FTS treatment significantly reduced BrdU incorporation and PCNA expression in hepatocytes after PH. Unlike control rats, cell-membrane expression of Ras was decreased in FTS-treated animals after PH, resulting in decreased Raf membrane recruitment and phosphorylation and in reduced phosphorylation of ERK1/2 (extracellular-signal-regulated kinase 1/2). The antiproliferative effect of FTS was linked to a decrease in expression and activity of the cyclin E/Cdk2 complex, without affecting cyclin D and Cdk4. Ras inhibition by FTS significantly decreased proliferation of HepG2 cells and normal hepatocytes after a strong and highly synchronized proliferation stimulus elicited by PH. The inhibitory effect was at least partially mediated by inhibition of Ras/Raf/MAPK signalling. It appears worthwhile to evaluate the impact of Ras inhibition on the development of hepatocarcinomas in vivo in adequate animal models