Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran; Cellular and Molecular Research Center, Birjand University of Medical Sciences, Birjand, Iran.
Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Life Sci. 2023 Aug 1;326:121813. doi: 10.1016/j.lfs.2023.121813. Epub 2023 May 29.
Aim Sepsis is a medical emergency with no definitive treatment. Animal experiments have confirmed the therapeutic characteristics of exosomes in reducing inflammation and tissue damage. The study investigates the effect of MSC and hepatocyte-derived exosomes along with imipenem in controlling systemic and local (liver) inflammation in a mouse model of sepsis.
To induce sepsis in C57BL/6 mice, the Cecal Ligation and Puncture (CLP) model was used. The mice were given various treatments, including imipenem, MSC-derived exosomes, hepatocyte-derived exosomes, and a mixture of exosomes. Blood and liver samples were collected and analyzed for cell blood count, liver enzymes, NO levels, cytokine concentrations, and bacterial presence. The percentages of TCD3 + CD4+/CD8+ and Treg in the spleen and mesenteric lymph nodes were also assessed using flow cytometry. The pathological changes were assessed in the liver, lung, and heart tissues. In addition, the cytokine content of exosomes was measured by ELISA.
Our results demonstrated that MSC-derived exosomes+imipenem could control systemic and local inflammation and increase the TCD4+ and Treg populations. Hepatocyte-derived exosomes+imipenem reduced inflammation in the liver and increased the TCD8+ and Treg populations. The mixture of exosomes+imipenem had the best function in reducing inflammation, maintaining all T lymphocyte populations, reducing liver damage, and ultimately increasing the survival rate.
The mixture of exosomes derived from MSCs and hepatocytes, along with imipenem, in the inflammatory phase of sepsis could be a promising therapeutic strategy in sepsis treatment.
败血症是一种没有明确治疗方法的医学急症。动物实验已经证实了外泌体在减轻炎症和组织损伤方面的治疗特性。本研究旨在探讨间充质干细胞（MSC）和肝细胞来源的外泌体与亚胺培南联合应用对败血症小鼠模型全身和局部（肝脏）炎症的控制作用。
采用盲肠结扎穿孔（CLP）模型诱导 C57BL/6 小鼠败血症。给予小鼠不同的治疗方法，包括亚胺培南、MSC 来源的外泌体、肝细胞来源的外泌体以及外泌体混合物。采集血液和肝脏样本，分析血细胞计数、肝酶、NO 水平、细胞因子浓度和细菌存在情况。使用流式细胞术评估脾和肠系膜淋巴结中 TCD3+CD4+/CD8+和 Treg 的百分比。评估肝脏、肺和心脏组织的病理变化。此外，通过 ELISA 测量外泌体的细胞因子含量。
我们的结果表明，MSC 来源的外泌体+亚胺培南可以控制全身和局部炎症，并增加 TCD4+和 Treg 群体。肝细胞来源的外泌体+亚胺培南可减轻肝脏炎症并增加 TCD8+和 Treg 群体。外泌体混合物+亚胺培南在减轻炎症、维持所有 T 淋巴细胞群体、减轻肝损伤和最终提高生存率方面具有最佳功能。
在败血症炎症期，MSC 和肝细胞来源的外泌体混合物与亚胺培南联合应用可能成为败血症治疗的一种有前途的治疗策略。
