title: Exosomal MicroRNAs Derived From Umbilical Mesenchymal Stem Cells Inhibit Hepatitis C Virus Infection.
abstract: : 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-α 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.
  
  
  
  This work reported, for the first time, the identification of stem cell-derived exosomes of antiviral activity. Umbilical mesenchymal stem cell-secreted exosomes inhibited hepatitis C virus infection through transporting a mixture of microRNAs complementing the viral genomes to the host cells. This finding provides insights and prospects for physiologically secreted substances for antiviral therapy.
authors: Department of Microbiology, Shanghai Key Laboratory of Medical Biodefense, Second Military Medical University, Shanghai, People's Republic of China.
authors: Xijing
authors: X
authors: Qian
authors: Department of Spinal Surgery, Changzheng Hospital Affiliated to Second Military Medical University, Shanghai, People's Republic of China.
authors: Chen
authors: C
authors: Xu
authors: Department of Plastic and Reconstruction, Changhai Hospital Affiliated to Second Military Medical University, Shanghai, People's Republic of China.
authors: Shuo
authors: S
authors: Fang
authors: Department of Microbiology, Shanghai Key Laboratory of Medical Biodefense, Second Military Medical University, Shanghai, People's Republic of China.
authors: Ping
authors: P
authors: Zhao
authors: Research Center of Developmental Biology, Second Military Medical University, Shanghai, People's Republic of China.
authors: Yue
authors: Y
authors: Wang
authors: Research Center of Developmental Biology, Second Military Medical University, Shanghai, People's Republic of China.
authors: Houqi
authors: H
authors: Liu
authors: Department of Spinal Surgery, Changzheng Hospital Affiliated to Second Military Medical University, Shanghai, People's Republic of China.
authors: Wen
authors: W
authors: Yuan
authors: Department of Microbiology, Shanghai Key Laboratory of Medical Biodefense, Second Military Medical University, Shanghai, People's Republic of China qizt@smmu.edu.cn.
authors: Zhongtian
authors: Z
authors: Qi
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D055354:Exosomes / Q000235:genetics*; D005312:Fetal Blood / Q000166:cytology; D005455:Fluorescent Antibody Technique; D016174:Hepacivirus; D006526:Hepatitis C / Q000188:drug therapy; D006801:Humans; D047468:Immunoprecipitation; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D035683:MicroRNAs / Q000494:pharmacology*; D016133:Polymerase Chain Reaction
chemical_list: D000998:Antiviral Agents; D035683:MicroRNAs
keywords: Antiviral therapy; Exosomes; Hepatitis C virus; MicroRNA; Umbilical mesenchymal stem cell