Department of Animal Biology, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran.
Department of Organic Chemistry, Tarbiat Modares University, Tehran, Iran.
Cell Prolif. 2021 Nov;54(11):e13126. doi: 10.1111/cpr.13126. Epub 2021 Sep 27.
Acute 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.
To provide a rat model of acute liver failure, male rats were injected intraperitoneally with carbon tetrachloride (CCl ). The rats were randomly divided into six groups, namely control, sham, CCl , 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 CCl and either ESC-MSC-CM with 5 × 10 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.
The 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 CCl -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.
Magnetic graphene oxide improved the hepatoprotective effects of ESC-MSC-CM on acute liver damage, probably by suppressing necrosis, apoptosis and inflammation of hepatocytes.
急性肝衰竭通常与肝细胞的炎症和氧化有关，具有高死亡率和资源成本。间充质干细胞（MSCs）由于移植和植入细胞的存活率差，偶尔被报道没有有益的效果。最近的研究表明，胚胎干细胞（ESC）衍生的MSCs是再生医学的一种替代方法。另一方面，基于石墨烯的纳米结构已被证明在生物医学中有应用。在本研究中，我们研究了磁性氧化石墨烯（MGO）是否能提高 ESC-MSC 条件培养基（CM）对保护肝细胞和刺激受损肝细胞再生的作用。
为了提供急性肝衰竭的大鼠模型，雄性大鼠腹膜内注射四氯化碳（CCl ）。大鼠随机分为六组，即对照组、假手术组、CCl 组、ESC-MSC-CM 组、MGO 组和 ESC-MSC-CM+MGO 组。在实验组中，根据组别，大鼠分别接受 2ml/kg 体重的 CCl 和 5×10 MSC 的 ESC-MSC-CM 或 300μg/kg 体重的 MGO 或两者。注射后 4 天出现急性肝衰竭症状。注射后 4 天，对所有组进行比较和分析，包括组织学和生化分析。最后，比较了 ESC-MSC-CM 和 MSC-CM 的结果。
结果表明，MGO 的使用增强了 ESC-MSC-CM 降低 CCl 诱导的大鼠模型肝衰竭中坏死、炎症、天冬氨酸转氨酶、丙氨酸转氨酶和碱性磷酸酶的作用。此外，用 MGO 处理后，血管内皮生长因子和基质金属蛋白酶-9（MMP-9）的表达明显上调。此外，结果表明 ESC-MSC-CM 比 MSC-CM 更有效。
磁性氧化石墨烯改善了 ESC-MSC-CM 对急性肝损伤的保护作用，可能通过抑制肝细胞的坏死、凋亡和炎症。
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