Exosomal MicroRNAs Derived From Umbilical Mesenchymal Stem Cells Inhibit Hepatitis C Virus Infection
Exosomal MicroRNAs Derived From Umbilical Mesenchymal Stem Cells Inhibit Hepatitis C Virus Infection
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脐带间充质干细胞衍生的外泌体 MicroRNA 抑制丙型肝炎病毒感染
DOI：
10.5966/sctm.2015-0348
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发表时间：
2016-09-01
影响因子：
6
通讯作者：
Qi, Zhongtian
中科院分区：
文献类型：
--
作者：
Qian, Xijing;Xu, Chen;Qi, Zhongtian
丙型肝炎病毒（HCV）是一个重大的全球公共卫生问题，每年造成35万多人死亡。尽管直接作用抗病毒药物的开发提高了HCV患者的持续病毒学应答率，但仍然迫切需要具有更高疗效、更好耐受性和更便宜生产成本的新型抗HCV药物。基于细胞的治疗，特别是其独特而强大的旁分泌能力，通过细胞外囊泡（如外泌体）将信息传递给其他细胞，已成为近年来最受欢迎的治疗方法之一。在我们的研究中，广泛用于再生医学的脐带间充质干细胞（uMSCs）分泌的外泌体在体外抑制HCV感染，特别是病毒复制，并且具有低细胞毒性。我们的分析显示，来自umsc衍生外泌体（uMSC-Exo）的microrna （mirna）具有独特的表达谱，这些功能性mirna主要由uMSC-Exo释放的let-7f、miR-145、miR-199a和miR-221代表，在很大程度上有助于抑制HCV RNA复制。靶标预测算法表明，这四种mirna在HCV RNA中具有结合位点。此外，uMSC-Exo疗法与美国食品和药物管理局（fda）批准的干扰素- α或telaprevir联合使用时显示出协同效应，增强了它们的抗hcv能力，从而提高了这些再生物质作为抗hcv治疗最佳佐剂的临床意义。
Hepatitis C virus (HCV) is a significant global public health problem, causing more than 350,000 deaths every year. Although the development of direct-acting antivirals has improved the sustained virological response rate in HCV patients, novel anti-HCV agents with higher efficacy as well as better tolerance and cheaper production costs are still urgently needed. Cell-based therapy, especially its unique and strong paracrine ability to transfer information to other cells via extracellular vesicles such as exosomes, has become one of the most popular therapeutic methods in recent years. In our study, exosomes secreted from umbilical mesenchymal stem cells (uMSCs), which are widely used in regenerative medicine, inhibited HCV infection in vitro, especially viral replication, with low cell toxicity. Our analysis revealed that microRNAs (miRNAs) from uMSC-derived exosomes (uMSC-Exo) had their unique expression profiles, and these functional miRNAs, mainly represented by let-7f, miR-145, miR-199a, and miR-221 released from uMSC-Exo, largely contributed to the suppression of HCV RNA replication. These four miRNAs possessed binding sites in HCV RNA as demonstrated by the target prediction algorithm. In addition, uMSC-Exo therapy showed synergistic effect when combined with U.S. Food and Drug Administration-approved interferon-alpha or telaprevir, enhancing their anti-HCV ability and thus improving the clinical significance of these regenerative substances for future application as optimal adjuvants of anti-HCV therapy.