INTRODUCTION Extracellular vesicles (EVs), especially stem cell-derived EVs, have emerged as a potential novel therapy for acute kidney injury (AKI). However, their effects remain incompletely understood. Therefore, we performed this meta-analysis to systematically review the efficacy of EVs on AKI in preclinical rodent models. METHODS We searched PubMed, EMBASE, and the Web of Science up to March 2019 to identify studies that reported the treatment effects of EVs in a rodent AKI model. The primary outcome was serum creatinine (Scr) levels. The secondary outcomes were the blood urea nitrogen (BUN) levels, renal injury score, percentage of apoptotic cells, and interleukin (IL)-10 and tumour necrosis factor (TNF)-α levels. Two authors independently screened articles based on the inclusion and exclusion criteria. The meta-analysis was conducted using RevMan 5.3 and R software. RESULTS Thirty-one studies (n = 552) satisfied the inclusion criteria. Pooled analyses demonstrated that the levels of Scr (SMD = - 3.71; 95% CI = - 4.32, - 3.10; P < 0.01), BUN (SMD = - 3.68; 95% CI = - 4.42, - 2.94; P < 0.01), and TNF-α (SMD = - 2.65; 95% CI = - 4.98, - 0.32; P < 0.01); the percentage of apoptotic cells (SMD = - 6.25; 95% CI = - 8.10, - 4.39; P < 0.01); and the injury score (SMD = - 3.90; 95% CI = - 5.26, - 2.53; P < 0.01) were significantly decreased in the EV group, and the level of IL-10 (SMD = 2.10; 95% CI = 1.18, 3.02; P < 0.01) was significantly increased. Meanwhile, no significant difference was found between stem cell-derived EVs and stem cells. CONCLUSION The present meta-analysis confirmed that EV therapy could improve renal function and the inflammatory response status and reduce cell apoptosis in a preclinical rodent AKI model. This provides important clues for human clinical trials on EVs.

中文翻译：

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临床前啮齿动物模型中急性肾损伤的细胞外囊泡：荟萃分析。

引言细胞外囊泡（EVs），尤其是干细胞衍生的EVs，已成为潜在的急性肾损伤（AKI）新疗法。但是，它们的作用仍未完全了解。因此，我们进行了这项荟萃分析，以系统地评估电动汽车对临床前啮齿动物模型中AKI的疗效。方法我们搜索了截至2019年3月的PubMed，EMBASE和Web of Science，以鉴定报告了在啮齿动物AKI模型中电动车的治疗效果的研究。主要结果是血清肌酐（Scr）水平。次要结果是血液尿素氮（BUN）水平，肾脏损伤评分，凋亡细胞百分比，白介素（IL）-10和肿瘤坏死因子（TNF）-α水平。两位作者根据纳入和排除标准独立筛选了文章。使用RevMan 5.3和R软件进行荟萃分析。结果31项研究（n = 552）满足纳入标准。汇总分析显示Scr（SMD =-3.71; 95％CI =-4.32，-3.10; P <0.01），BUN（SMD =-3.68; 95％CI =-4.42，-2.94; P <0.01） ；和TNF-α（SMD ＝ -2.65； 95％CI ＝ -4.98，-0.32； P ＜0.01）。凋亡细胞的百分比（SMD =-6.25; 95％CI =-8.10，-4.39; P <0.01）; EV组的损伤评分（SMD =-3.90; 95％CI =-5.26，-2.53; P <0.01）显着降低，IL-10水平（SMD = 2.10; 95％CI = 1.18， 3.02； P <0.01）显着增加。同时，干细胞来源的电动汽车和干细胞之间没有发现显着差异。结论本荟萃分析证实，EV疗法可改善临床前啮齿动物AKI模型的肾功能和炎症反应状态并减少细胞凋亡。这为电动汽车的人体临床试验提供了重要的线索。