Magnetic Fe3O4@graphene oxide improves the therapeutic effects of embryonic stem cells on acute liver damage |
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Authors: | Tahereh Foroutan Mohammad Zaman Kassaee Mahdi Salari Fatemeh Ahmady Fatemeh Molavi Fariborz Moayer |
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Institution: | 1. Department of Animal Biology, Faculty of Biological Sciences, Kharazmi University, Tehran Iran ; 2. Department of Organic Chemistry, Tarbiat Modares University, Tehran Iran ; 3. Department of Environmental Health Engineering, School of Public Health, Hamadan University of Medical Sciences, Hamadan Iran ; 4. Faculty of Veterinary Medicine, Islamic Azad University, Karaj Iran |
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Abstract: | ObjectiveAcute liver failure is usually associated with inflammation and oxidation of hepatocytes and has high mortality and resource costs. Mesenchymal stem cell (MSCs) has occasionally been reported to have no beneficial effect due to poor transplantation and the survival of implanted cells. Recent studies showed that embryonic stem cell (ESC)‐derived MSCs are an alternative for regenerative medicine. On the other hand, graphene‐based nanostructures have proven useful in biomedicine. In this study, we investigated whether magnetic graphene oxide (MGO) improved the effects of ESC‐MSC conditioned medium (CM) on protecting hepatocytes and stimulating the regeneration of damaged liver cells.Materials and methodsTo provide a rat model of acute liver failure, male rats were injected intraperitoneally with carbon tetrachloride (CCl4). The rats were randomly divided into six groups, namely control, sham, CCl4, ESC‐MSC‐CM, MGO and ESC‐MSC‐CM + MGO. In the experimental groups, the rats received, depending on the group, 2 ml/kg body weight CCl4 and either ESC‐MSC‐CM with 5 × 106 MSCs or 300 μg/kg body weight MGO or both. Symptoms of acute liver failure appeared 4 days after the injection. All groups were compared and analysed both histologically and biochemically 4 days after the injection. Finally, the results of ESC‐MSC‐CM and MSC‐CM were compared.ResultsThe results indicated that the use of MGO enhanced the effect of ESC‐MSC‐CM on 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 MGO. Also, the results showed that the ESC‐MSC‐CM has more efficient effective compared to MSC‐CM.ConclusionMagnetic graphene oxide improved the hepatoprotective effects of ESC‐MSC‐CM on acute liver damage, probably by suppressing necrosis, apoptosis and inflammation of hepatocytes. |
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Keywords: | acute liver failure angiogenesis conditioned medium magnetic graphene oxide stem cell therapy |
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