Umbilical Cord Mesenchymal-Stem-Cell-Derived Exosomes Exhibit Anti-Oxidant and Antiviral Effects as Cell-Free Therapies

• Published in: Viruses Vol. 15; no. 10; p. 2094
• Main Authors: Meng, Yi, Li, Chengcheng, Liang, Yicong, Jiang, Yu, Zhang, Haonan, Ouyang, Jianhua, Zhang, Wen, Deng, Rumei, Tan, Qiuping, Yu, Xiaolan, Luo, Zhen
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 01.10.2023; MDPI
• Subjects: Aging; Antibodies; Antioxidants; antiviral activity; Antiviral agents; Antiviral drugs; c-Jun protein; Care and treatment; Cell death; Cell growth; Cell organelles; cell-free therapy; chronic diseases; death; enterovirus; Enterovirus A; Exosomes; Fibroblasts; genes; GTP-binding protein; Health aspects; Hydrogen peroxide; Immunogenicity; Infections; JNK protein; Kinases; Laboratories; MAP kinase; Mesenchymal stem cells; Mitochondrial DNA; mitogen-activated protein kinase; muscles; Musculoskeletal system; NF-κB protein; Oxidants; oxidative damage; Oxidative stress; protein synthesis; Proteins; Reactive oxygen species; Rhabdomyosarcoma; Senescence; Skeletal muscle; Skin; Stem cells; therapeutics; Therapeutics, Experimental; Transcription factors; Umbilical cord; umbilical cord mesenchymal stem cells (ucMSCs); Virus diseases; China; United States > US
• DOI: 10.3390/v15102094
• ISSN: 1999-4915

The oxidative stress induced by the accumulation of reactive oxygen species (ROS) can lead to cell aging and death. Equally, the skeletal muscle usually hosts enteroviral persistent infection in inflammatory muscle diseases. As excellent bioactive products, the exosomes derived from umbilical cord mesenchymal stem cells (ucMSCs) have been proven to be safe and have low immunogenicity with a potential cell-free therapeutic function. Here, exosomes derived from ucMSCs (ucMSC-EXO) were extracted and characterized. In a model of oxidative damage to skin fibroblasts (HSFs) under exposure to H2O2, ucMSC-EXO had an observable repairing effect for the HSFs suffering from oxidative damage. Furthermore, ucMSC-EXO inhibited mitogen-activated protein kinases (MAPK), c-Jun N-terminal kinase (JNK), and nuclear factor kappa-B (NF-κB) signaling pathways, thereby promoting p21 protein expression while decreasing lamin B1 protein expression, and finally alleviated oxidative stress-induced cell damage and aging. In a model of rhabdomyosarcoma (RD) cells being infected by enterovirus 71 (EV71) and coxsackievirus B3 (CVB3), the ucMSC-EXO enhanced the expression of interferon-stimulated gene 15 (ISG15) and ISG56 to inhibit enteroviral replication, whereafter reducing the virus-induced proinflammatory factor production. This study provides a promising therapeutic strategy for ucMSC-EXO in anti-oxidative stress and antiviral effects, which provides insight into extending the function of ucMSC-EXO in cell-free therapy.