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Wharton's Jelly Mesenchymal Stem Cell-Derived Extracellular Vesicles Reduce SARS-CoV2-Induced Inflammatory Cytokines Under High Glucose and Uremic Toxin Conditions
Stem Cells and Development ( IF 2.5 ) Pub Date : 2021-08-02 , DOI: 10.1089/scd.2021.0065
Vuong Cat Khanh 1 , Mizuho Fukushige 1 , Yun Hsuan Chang 1 , Ngo Nhat Hoang 1 , Toshiharu Yamashita 1 , Mana Obata-Yasuoka 2 , Hiromi Hamada 2 , Motoo Osaka 3 , Yuji Hiramatsu 3 , Osamu Ohneda 1
Affiliation  

Cytokine storm is recognized as one of the factors contributing to organ failures and mortality in patients with COVID-19. Due to chronic inflammation, COVID-19 patients with diabetes mellitus (DM) or renal disease (RD) have more severe symptoms and higher mortality. However, the factors that contribute to severe outcomes of COVID-19 patients with DM and RD have received little attention. In an effort to investigate potential treatments for COVID-19, recent research has focused on the immunomodulation functions of mesenchymal stem cells (MSCs). In this study, the correlation between DM and RD and the severity of COVID-19 was examined by a combined approach with a meta-analysis and experimental research. The results of a systematic review and meta-analysis suggested that the odd of mortality in patients with both DM and RD was increased in comparison to those with a single comorbidity. In addition, in the experimental research, the data showed that high glucose and uremic toxins contributed to the induction of cytokine storm in human lung adenocarcinoma epithelial cells (Calu-3 cells) in response to SARS-CoV Peptide Pools. Of note, the incorporation of Wharton's jelly MSC-derived extracellular vesicles (WJ-EVs) into SARS-CoV peptide-induced Calu-3 resulted in a significant decrease in nuclear NF-κB p65 and the downregulation of the cytokine storm under high concentrations of glucose and uremic toxins. This clearly suggests the potential for WJ-EVs to reduce cytokine storm reactions in patients with both chronic inflammation diseases and viral infection.

中文翻译:


沃顿商学院的果冻间充质干细胞来源的细胞外囊泡可减少高血糖和尿毒症毒素条件下 SARS-CoV2 诱导的炎症细胞因子



细胞因子风暴被认为是导致 COVID-19 患者器官衰竭和死亡的因素之一。由于慢性炎症,患有糖尿病(DM)或肾病(RD)的COVID-19患者症状更严重,死亡率更高。然而,导致患有 DM 和 RD 的 COVID-19 患者出现严重后果的因素却很少受到关注。为了研究 COVID-19 的潜在治疗方法,最近的研究重点是间充质干细胞 (MSC) 的免疫调节功能。在这项研究中,通过荟萃分析和实验研究相结合的方法检查了 DM 和 RD 与 COVID-19 严重程度之间的相关性。系统评价和荟萃分析的结果表明,与单一合并症患者相比,同时患有 DM 和 RD 的患者的死亡率有所增加。此外,在实验研究中,数据显示,高葡萄糖和尿毒症毒素有助于诱导人肺腺癌上皮细胞(Calu-3细胞)响应SARS-CoV肽库而产生细胞因子风暴。值得注意的是,将沃顿胶 MSC 衍生的细胞外囊泡 (WJ-EV) 掺入 SARS-CoV 肽诱导的 Calu-3 中,导致核 NF-κB p65 显着降低,并在高浓度的条件下下调细胞因子风暴。葡萄糖和尿毒症毒素。这清楚地表明 WJ-EV 有可能减少慢性炎症性疾病和病毒感染患者的细胞因子风暴反应。
更新日期:2021-08-03
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