Liver fibrosis

and hepatic stellate cell (HSC) activation

Liver fibrosis

and hepatic stellate cell (HSC) activation were assessed by sirius red staining and immunohistochemistry. Injury serum markers such as alanine transaminase (ALT), aspartate transam-inase (AST), and total antioxidant activity were evaluated. To confirm the protective effects against oxidant conditions, we used hydrogen peroxide or thioacetamide in order to induce oxidative stress conditions in vitro. We then quantified cellular reactive oxygen species (ROS) and enzymes related to oxidative stress resolution in HSCs and hepatocytes co-cultured with MSCs. Results: We confirmed that our cells showed MSC characteristics. They were adherent to plastic, positive for CD73/CD90/CD105 and negative for CD45, and were able to differentiate into adipocytes I-BET-762 nmr and osteocytes. In NOD-SCID cirrhotic mice, they were able to reduce liver fibrosis

(p<0.05) and hepatic αSMA-positive area (p<0.05). In addition, mice treated with MSCs showed lower R788 price levels of ALT (p<0.05) and AST (p<0.05), and higher total antioxidant activity (p<0.001). HSCs co-cultured with MSCs showed lower levels of ROS (p<0.05), consistent with up-regulated expressions of heme oxy-genase-1 (p<0.01) and superoxide dismutase-3 (p<0.001) in MSCs. Moreover, we confirmed that hepatocytes co-cultured with MSCs had lower levels of ROS (p<0.001), and higher expressions of NF-E2-related factor 2 (p<0.05) and glutathione S-transferase (p<0.01). Conclusions: These results demonstrate that infused MSCs are involved in the improvement of liver injury through stabilization of redox homeostasis, which strongly indicates the possibility of a less invasive

liver regeneration therapy for liver cirrhotic patients using cultured autologous BM-derived MSCs. Disclosures: The following people have nothing to disclose: CYTH4 Taro Takami, Shuji Terai, Luiz Fernando Quintanilha, Koichi Fujisawa, Naoki Yamamoto, Isao Sakaida As hepatic fibrosis progresses, elastin content and matrix crosslinking increase. This may limit reversibility of cirrhosis. Aims: 1 )develop an automated image analysis algorithm to quantify elastin in immunostained biopsies; 2)evaluate elastin as a predictor of clinical outcomes from cirrhosis due to CHC. Patients with a biopsy showing Ishak stage (IS) 5 or 6 fibrosis were selected from 1 centre within the Trent Study of Patients with Hepatitis C Virus Infection. An elastin-specific antibody (Abcam ab21610) was used for quantitative immunohisto-chemistry. A digital image analysis algorithm was developed with ImageJ software (NIH). The algorithm uses statistical colour modelling to avoid a need for manual thresholding and is an automated process. We evaluated hepatic elastin as a predictor of subsequent clinical outcomes, defined as the first event of variceal bleed, ascites, encephalopathy, hepatocellular carcinoma, liver transplantation or liver-related death. 48 patients were included (IS5: n=27; IS6: n=21).

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