Abstract：
BACKGROUND: Sepsis is a life-threatening disorder with no definitive cure. Preclinical studies suggest that extracellular vesicles derived from mesenchymal stromal cells (EV-MSCs) can mitigate inflammatory conditions, potentially leading to increased survival and reduced organ dysfunction during sepsis. Our aim to conduct this systematic review and meta-analysis is assessing the EV-MSCs therapeutic efficacy in sepsis.
METHODS: PubMed, Embase, Scopus, WOS and ProQuest databases and also Google Scholar search engine were searched for published articles. We used hazard ratio (HR) and standardized mean difference (SMD) as effect sizes to evaluate the therapeutic effect of EV-MSCs on survival rate and determine their effect on reducing organ dysfunction, respectively. Finally, we employed GRADE tool for preclinical animal studies to evaluate certainty of the evidence.
RESULTS: 30 studies met the inclusion criteria for our article. Our meta-analysis results demonstrate that animals treated with MSC-EVs have better survival rate than untreated animals (HR = 0.33; 95% CI: 0.27-0.41). Our meta-analysis suggests that EV-MSCs can reduce organ dysfunctions in sepsis, such as the lung, kidney, and liver. Additionally, EV-MSCs decrease pro-inflammatory mediators like TNF-α, IL-1β, and IL-6.
CONCLUSIONS: Our results indicate that EV-MSCs can be as promising therapy for sepsis management in animal models and leading to increased survival rate and reduced organ dysfunction. Furthermore, our study introduces a novel tool for risk of bias assessment and provides recommendations based on various analysis. Future studies with aiming to guide clinical translation can utilize the results of this article to establish stronger evidence for EV-MSC effectiveness.
METHODS: PubMed, Embase, Scopus, WOS and ProQuest databases and also Google Scholar search engine were searched for published articles. We used hazard ratio (HR) and standardized mean difference (SMD) as effect sizes to evaluate the therapeutic effect of EV-MSCs on survival rate and determine their effect on reducing organ dysfunction, respectively. Finally, we employed GRADE tool for preclinical animal studies to evaluate certainty of the evidence.
RESULTS: 30 studies met the inclusion criteria for our article. Our meta-analysis results demonstrate that animals treated with MSC-EVs have better survival rate than untreated animals (HR = 0.33; 95% CI: 0.27-0.41). Our meta-analysis suggests that EV-MSCs can reduce organ dysfunctions in sepsis, such as the lung, kidney, and liver. Additionally, EV-MSCs decrease pro-inflammatory mediators like TNF-α, IL-1β, and IL-6.
CONCLUSIONS: Our results indicate that EV-MSCs can be as promising therapy for sepsis management in animal models and leading to increased survival rate and reduced organ dysfunction. Furthermore, our study introduces a novel tool for risk of bias assessment and provides recommendations based on various analysis. Future studies with aiming to guide clinical translation can utilize the results of this article to establish stronger evidence for EV-MSC effectiveness.
摘要：
背景：脓毒症是一种威胁生命的疾病，没有明确的治疗方法。临床前研究表明，源自间充质基质细胞（EV-MSCs）的细胞外囊泡可以缓解炎症，可能导致脓毒症期间存活率增加和器官功能障碍减少。我们的目的是进行系统评价和荟萃分析，评估EV-MSCs在脓毒症中的治疗效果。
方法：PubMed，Embase,Scopus,搜索了WOS和ProQuest数据库以及GoogleScholar搜索引擎以查找已发表的文章。我们使用风险比（HR）和标准化平均差异（SMD）作为效应大小来评估EV-MSCs对存活率的治疗效果，并确定其对减少器官功能障碍的作用。分别。最后,我们使用GRADE工具进行临床前动物研究,以评估证据的确定性.
结果：30项研究符合我们文章的纳入标准。我们的荟萃分析结果表明，用MSC-EV治疗的动物比未经治疗的动物具有更好的存活率（HR=0.33;95％CI：0.27-0.41）。我们的荟萃分析表明，EV-MSCs可以减少脓毒症的器官功能障碍，比如肺，肾,还有肝脏.此外,EV-MSCs减少促炎介质，如TNF-α，IL-1β,IL-6
结论：我们的结果表明，EV-MSCs可以作为动物模型中败血症治疗的有希望的治疗方法，并导致存活率增加和器官功能障碍减少。此外，我们的研究引入了一种新的偏倚风险评估工具,并基于各种分析提供了建议.未来旨在指导临床翻译的研究可以利用本文的结果为EV-MSC有效性建立更强有力的证据。
方法：PubMed，Embase,Scopus,搜索了WOS和ProQuest数据库以及GoogleScholar搜索引擎以查找已发表的文章。我们使用风险比（HR）和标准化平均差异（SMD）作为效应大小来评估EV-MSCs对存活率的治疗效果，并确定其对减少器官功能障碍的作用。分别。最后,我们使用GRADE工具进行临床前动物研究,以评估证据的确定性.
结果：30项研究符合我们文章的纳入标准。我们的荟萃分析结果表明，用MSC-EV治疗的动物比未经治疗的动物具有更好的存活率（HR=0.33;95％CI：0.27-0.41）。我们的荟萃分析表明，EV-MSCs可以减少脓毒症的器官功能障碍，比如肺，肾,还有肝脏.此外,EV-MSCs减少促炎介质，如TNF-α，IL-1β,IL-6
结论：我们的结果表明，EV-MSCs可以作为动物模型中败血症治疗的有希望的治疗方法，并导致存活率增加和器官功能障碍减少。此外，我们的研究引入了一种新的偏倚风险评估工具,并基于各种分析提供了建议.未来旨在指导临床翻译的研究可以利用本文的结果为EV-MSC有效性建立更强有力的证据。
