Here, we evaluated the role of BMSCs in liver regeneration and the underlying mechanisms. Methods: To assess the effects of cultured BMSCs on liver cirrhosis, BAY 57-1293 we systemically infused BMSCs into thioacetamide-induced NOD-SCID cirrhotic mice. Liver fibrosis and antioxidant effects were assessed with Sirius red staining and a kinetic study of inhibition of diammonium salt oxidation. We also screened the profile of microRNAs in BMSC-infused livers using a miRNA array. We used thioacetamide to induce oxidative stress in vitro and confirmed the protective effects of BMSCs or exosomes derived
from BMSCs on oxidant conditions. We then measured cellular reactive oxygen species (ROS) and factors related to oxidative stress resolution in hepatocytes co-cultured with BMSCs or their exosomes. Results: BMSC-infused NOD-SCID mice showed reduced liver fibrosis (p<0.05), higher serum antioxidant activity (p<0.001), lower levels of hepatic malondialdehyde (p<0.05) and significantly higher amounts of hepatic miR-200a-3p, Rucaparib solubility dmso which targets Keap1 mRNA (ratio 3.67 vs. controls). Hepatocytes co-cultured with not only BMSCs, but also their
exosomes, showed lower levels of ROS (p<0.001). Hepatocytes in which the miR-200a-3p target site was blocked showed significantly higher levels of ROS, despite supplementation with exosomes of BMSCs in vitro. Conclusions: These results suggest that the selleck chemicals llc infusion of cultured BMSCs secreting exosomes, including miR-200a-3p, helped to improve liver fibrosis by stabilizing redox homeostasis. This indicates that a less invasive liver regeneration therapy for liver cirrhotic
patients using cultured autologous BMSCs is highly possible. Disclosures: Shuji Terai – Speaking and Teaching: Otsuka Pharma. The following people have nothing to disclose: Taro Takami, Luiz Fernando Quintanilha, Bruno D. Paredes, Koichi Fujisawa, Naoki Yamamoto, Isao Sakaida [Background/Aims] Recently, we identified a novel liver fibrosis glycobiomarker Wisteria floribunda agglutinin (WFA)-reactive colony stimulating factor 1 receptor (WFA+-CSF1R) using a glycoproteomics-based strategy. Elevated expression of CSF1R has been reported in a variety of malignancies of epithelial origin, including breast, prostate, and ovarian carcinomas. The aim of the present study was to assess the utility of measuring WFA+-CSF1R levels for hepatocarcinogenesis and outcome in patients with liver cirrhosis (LC). [Methods] WFA+-CSF1R and total CSF1R levels were measured by an antibody-lectin sandwich ELISA in serum samples from 207 consecutive hepatitis C virus (HCV)-infected patients from 1998 to 2013 in order to evaluate impact on carcinogenesis and survival of LC patients. The median age was 64 (21-87) and male was 110 (53.1%).