Mesenchymal stem cell (MSC) transplantation was shown to be effective for the treatment of liver fibrosis, but the mechanisms of action are not yet fully understood. We transplanted encapsulated human MSCs in two mouse models of liver fibrosis to determine the mechanisms behind the protective effect. Human bone marrow-derived MSCs were microencapsulated in novel alginate-polyethylene glycol microspheres. In vitro, we analyzed the effect of MSC-conditioned medium on the activation of hepatic stellate cells and the viability, proliferation, cytokine secretion, and differentiation capacity of encapsulated MSCs. The level of fibrosis induced by bile duct ligation (BDL) or carbon tetrachloride (CCl4) was assessed after intraperitoneal transplantation of encapsulated MSCs, encapsulated human fibroblasts, and empty microspheres. MSC-conditioned medium inhibited hepatic stellate cell activation and release of MSC secreted anti-apoptotic (IL-6, IGFBP-2) and anti-inflammatory (IL-1Ra) cytokines. Viability, proliferation, and cytokine secretion of microencapsulated MSCs were similar to those of non-encapsulated MSCs. Within the microspheres, MSCs maintained their capacity to differentiate into adipocytes, chondrocytes, and osteocytes. 23% (5/22) of the MSC clones were able to produce anti-inflammatory IL-1Ra in vitro. Microencapsulated MSCs significantly delayed the development of BDL- and CCl4-induced liver fibrosis. Fibroblasts had an intermediate effect against CCl4-induced fibrosis. Mice transplanted with encapsulated MSCs showed lower mRNA levels of collagen type I, whereas levels of matrix metalloproteinase 9 were significantly higher. Human IL-1Ra was detected in the serum of 36% (4/11) of the mice transplanted with microencapsulated MSCs. MSC-derived soluble molecules are responsible for an anti-fibrotic effect in experimental liver fibrosis.

Reducing anastomotic leak in colorectal surgery: The old dogmas and the new challenges

Objective: This study aimed to determine which bariatric procedure allows patients to obtain the best weight‐loss outcomes and a remission of type 2 diabetes.Methods: Databases were searched for randomized‐controlled trials comparing Roux‐en‐Y gastric bypass (RYGB) with sleeve gastrectomy (SG) or one‐anastomosis gastric bypass (OAGB). The mean difference (MD) or the relative risk was determined.Results: Twenty‐five randomized‐controlled trials were analyzed. Excess weight loss (EWL, percentage) was greater for RYGB patients at 3 years (MD: 11.93, p < 0.00001) and 5 years (MD: 13.11, p = 0.0004). Higher excess BMI loss (percentage) was found in RYGB at 1 year (MD: 11.66, p = 0.01). Total weight loss (percentage) was greater for RYGB patients after 3 months (MD: 2.41, p = 0.02), 6 months (MD: 3.83, p < 0.00001), 1 year (MD: 6.35, p < 0.00001), and 5 years (MD: 3.90, p = 0.005). No difference in terms of remission of type 2 diabetes was seen between RYGB and SG. EWL was significantly more important after OAGB than after RYGB after 1 year (MD: −10.82, p = 0.003).Conclusions: RYGB is more efficient than SG in the midterm. OAGB offers greater EWL than RYGB after 1 year, but further evidence is needed to confirm this result.

Background: Interleukin-1 (IL-1)β and IL-1 receptor antagonist (IL-1Ra) have been proposed as important mediators during chronic liver diseases. We aimed to determine whether the modulation of IL-1β signaling with IL-1Ra impacts on liver fibrosis. Methods: We assessed the effects of IL-1β on human hepatic stellate cells (HSC) and in mouse models of liver fibrosis induced by bile duct ligation (BDL) or carbon tetrachloride treatment (CCl-4). Results: Human HSCs treated with IL-1β had increased IL-1β, IL-1Ra, and MMP-9 expressions in vitro. HSCs treated with IL-1β had reduced α-smooth muscle actin expression. These effects were all prevented by IL-1Ra treatment. In the BDL model, liver fibrosis and Kuppfer cell numbers were increased in IL-1Ra KO mice compared to wild type mice and wild type mice treated with IL-1Ra. In contrast, after CCl-4 treatment, fibrosis, HSC and Kupffer cell numbers were decreased in IL-1Ra KO mice compared to the other groups. IL-1Ra treatment provided a modest protective effect in the BDL model and was pro-fibrotic in the CCl-4 model. Conclusions: We demonstrated bivalent effects of IL-1Ra during liver fibrosis in mice. IL-1Ra was detrimental in the CCl-4 model, whereas it was protective in the BDL model. Altogether these data suggest that blocking IL-1-mediated inflammation may be beneficial only in selective liver fibrotic disease.