Therapeutic potential of mesenchymal stem cell-derived extracellular vesicles in SARS-CoV-2 and H1N1 influenza-induced acute lung injury

IF 15.5 1区 医学 Q1 CELL BIOLOGY
Jun Ho Lee, Hyungtaek Jeon, Jan Lötvall, Byong Seung Cho
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Abstract

Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) have shown anti-inflammatory potential in multiple inflammatory diseases. In the March 2022 issue of the Journal of Extracellular Vesicles, it was shown that EVs from human MSCs can suppress severe acute respiratory distress syndrome, coronavirus 2 (SARS-CoV-2) replication and can mitigate the production and release of infectious virions. We therefore hypothesized that MSC-EVs have an anti-viral effect in SARS-CoV-2 infection in vivo. We extended this question to ask whether also other respiratory viral infections could be treated by MSC-EVs. Adipose stem cell-derived EVs (ASC-EVs) were isolated using tangential flow filtration from conditioned media obtained from a multi-flask cell culture system. The effects of the ASC-EVs were tested  in Vero E6 cells in vitro. ASC-EVs were also given i.v. to SARS-CoV-2 infected Syrian Hamsters, and H1N1 influenza virus infected mice. The ASC-EVs attenuated SARS-CoV-2 virus replication in Vero E6 cells and reduced body weight and signs of lung injury in infected Syrian hamsters. Furthermore, ASC-EVs increased the survival rate of influenza A-infected mice and attenuated signs of lung injury. In summary, this study suggests that ASC-EVs can have beneficial therapeutic effects in models of virus-infection-associated acute lung injury and may potentially be developed to treat lung injury in humans.

Abstract Image

间充质干细胞衍生的细胞外囊泡在 SARS-CoV-2 和 H1N1 流感诱发的急性肺损伤中的治疗潜力
间充质干细胞(MSC)衍生的细胞外囊泡(EVs)已在多种炎症疾病中显示出抗炎潜力。2022年3月出版的《细胞外囊泡杂志》(Journal of Extracellular Vesicles)显示,来自人类间充质干细胞的细胞外囊泡能抑制严重急性呼吸窘迫综合征冠状病毒2(SARS-CoV-2)的复制,并能减轻传染性病毒的产生和释放。因此,我们假设间充质干细胞-EVs 在体内感染 SARS-CoV-2 时具有抗病毒作用。我们将这一问题延伸至间叶干细胞-EV是否也能治疗其他呼吸道病毒感染。我们使用切向流过滤法从多层细胞培养系统获得的条件培养基中分离出了脂肪干细胞衍生的EVs(ASC-EVs)。在体外 Vero E6 细胞中测试了 ASC-EVs 的作用。此外,还为感染了 SARS-CoV-2 的叙利亚仓鼠和感染了 H1N1 流感病毒的小鼠静脉注射了 ASC-EV。ASC-EVs 可减轻 SARS-CoV-2 病毒在 Vero E6 细胞中的复制,减轻受感染叙利亚仓鼠的体重和肺损伤症状。此外,ASC-EVs 还能提高甲型流感感染小鼠的存活率,减轻肺损伤症状。总之,这项研究表明,ASC-EVs 可在病毒感染相关急性肺损伤模型中产生有益的治疗效果,并有可能开发用于治疗人类肺损伤。
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来源期刊
Journal of Extracellular Vesicles
Journal of Extracellular Vesicles Biochemistry, Genetics and Molecular Biology-Cell Biology
CiteScore
27.30
自引率
4.40%
发文量
115
审稿时长
12 weeks
期刊介绍: The Journal of Extracellular Vesicles is an open access research publication that focuses on extracellular vesicles, including microvesicles, exosomes, ectosomes, and apoptotic bodies. It serves as the official journal of the International Society for Extracellular Vesicles and aims to facilitate the exchange of data, ideas, and information pertaining to the chemistry, biology, and applications of extracellular vesicles. The journal covers various aspects such as the cellular and molecular mechanisms of extracellular vesicles biogenesis, technological advancements in their isolation, quantification, and characterization, the role and function of extracellular vesicles in biology, stem cell-derived extracellular vesicles and their biology, as well as the application of extracellular vesicles for pharmacological, immunological, or genetic therapies. The Journal of Extracellular Vesicles is widely recognized and indexed by numerous services, including Biological Abstracts, BIOSIS Previews, Chemical Abstracts Service (CAS), Current Contents/Life Sciences, Directory of Open Access Journals (DOAJ), Journal Citation Reports/Science Edition, Google Scholar, ProQuest Natural Science Collection, ProQuest SciTech Collection, SciTech Premium Collection, PubMed Central/PubMed, Science Citation Index Expanded, ScienceOpen, and Scopus.
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