Department of Emergency, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, 518003, Guangdong, People's Republic of China.
Department of Emergency, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, 510120, Guangdong, People's Republic of China.
J Transl Med. 2023 Apr 17;21(1):262. doi: 10.1186/s12967-023-04121-7.
Multiple preclinical studies have reported a beneficial effect of extracellular vesicles (EVs), especially mesenchymal stem cells derived EVs (MSC-EVs), in the treatment of sepsis. However, the therapeutic effect of EVs is still not universally recognized. Therefore, we conducted this meta-analysis by summarizing data from all published studies that met certain criteria to systematically review the association between EVs treatment and mortality in animal models of sepsis.
Systematic retrieval of all studies in PubMed, Cochrane and Web of Science that reported the effects of EVs on sepsis models up to September 2022. The primary outcome was animal mortality. After screening the eligible articles according to inclusion and exclusion criteria, the inverse variance method of fixed effect model was used to calculate the joint odds ratio (OR) and 95% confidence interval (CI). Meta-analysis was performed by RevMan version 5.4.
In total, 17 studies met the inclusion criteria. Meta-analysis of those studies showed that EVs treatment was associated with reduced mortality in animal models of sepsis (OR 0.17 95% CI: 0.11,0.26, P < 0.001). Further subgroup analysis showed that the mode of sepsis induction, the source, dose, time and method of injection, and the species and gender of mice had no significant effect on the therapeutic effect of EVs.
This meta-analysis showed that MSC-EVs treatment may be associated with lower mortality in animal models of sepsis. Subsequent preclinical studies will need to address the standardization of dose, source, and timing of EVs to provide comparable data. In addition, the effectiveness of EVs in treating sepsis must be studied in large animal studies to provide important clues for human clinical trials.
多项临床前研究报告称，细胞外囊泡（EVs），尤其是间充质干细胞衍生的 EVs（MSC-EVs），在治疗脓毒症方面具有有益作用。然而，EVs 的治疗效果仍未得到普遍认可。因此，我们通过总结所有符合一定标准的已发表研究数据，进行了这项荟萃分析，以系统地评估 EVs 治疗与脓毒症动物模型死亡率之间的关联。
系统检索截至 2022 年 9 月在 PubMed、Cochrane 和 Web of Science 上发表的所有报告 EVs 对脓毒症模型影响的研究。主要结局是动物死亡率。根据纳入和排除标准筛选合格文献后，采用固定效应模型的Inverse variance 方法计算联合优势比（OR）和 95%置信区间（CI）。采用 RevMan 版本 5.4 进行荟萃分析。
共有 17 项研究符合纳入标准。这些研究的荟萃分析表明，EVs 治疗与脓毒症动物模型死亡率降低相关（OR 0.17，95%CI：0.11，0.26，P<0.001）。进一步的亚组分析表明，脓毒症诱导方式、来源、剂量、时间和注射方式以及小鼠的种属和性别对 EVs 的治疗效果没有显著影响。
这项荟萃分析表明，MSC-EVs 治疗可能与降低脓毒症动物模型的死亡率相关。随后的临床前研究需要解决 EVs 的剂量、来源和时间的标准化问题，以提供可比的数据。此外，必须在大动物研究中研究 EVs 治疗脓毒症的有效性，为人类临床试验提供重要线索。
