Silica Magnetic Graphene Oxide Improves the Effects of Stem Cell-Conditioned Medium on Acute Liver Failure.

Abstract

Objective: Acute liver failure (ALF) is usually associated with inflammation and oxidation of hepatocytes and has high mortality and resource costs. Although mesenchymal stem cell-conditioned medium (MSC-CM) has therapeutic effects similar to MSC transplant in treating liver failure, it may not increase survival. On the other hand, graphene-based nanostructures have been proven useful in biomedicine. In this study, we investigated whether silica magnetic graphene oxide (SMGO) improved the effects of MSC-CM in protecting hepatocytes and stimulating the regeneration of damaged liver cells. Materials and methods: To provide a rat model of ALF, male rats were injected intraperitoneally with carbon tetrachloride (CCl4). The rats were randomly divided into six groups, namely control, sham, CCl4, MSC-CM, SMGO, and MSC-CM + SMGO. In the experimental groups, the rats received, depending on the group, 2 mL/kg body weight CCl4 and either MSC-CM with 5 × 106 MSCs or 300 μg/kg body weight SMGO or both. Symptoms of ALF appeared 4 days after the injection. All groups were compared and analyzed both histologically and biochemically 4 days after the injection. Results: The results indicated that the use of SMGO enhanced the effect of MSC-CM in reducing necrosis, inflammation, aspartate transaminase, alanine aminotransferase, and alkaline phosphatase in the CCl4-induced liver failure of the rat model. Also, the expression of vascular endothelial growth factor and matrix metalloproteinase-9 (MMP-9) was significantly upregulated after treatment with SMGO. Conclusion: SMGO improved the hepatoprotective effects of MSC-CM on acute liver damage, probably by suppressing necrosis, apoptosis, and inflammation of hepatocytes.