Given that the modification of stem cell-derived extracellular vesicles (EVs) can enhance their regenerative efficiency, an increasing number of studies pay attention to the therapeutic potential of hypoxic preconditioning of stem cell-derived EVs (Hypo-EVs) in cardiac repair. Our meta-analysis aims to evaluate the cardiac repair of Hypo-EVs in preclinical animal models of myocardial infarction (MI). We searched PubMed, EMBASE, and the Web of Science up to January 2021. The primary outcome was left ventricular ejection fraction (LVEF). The second outcomes were left ventricular fractional shortening (LVFS) and infarct size. Random-effects modeling was used to calculate pooled weighted mean differences (WMDs) and 95% confidence intervals (CIs). Nine studies satisfied the inclusion criteria. Compared with the model group, pooled analyses demonstrated that stem cell-derived EVs culturing in normal oxygen environment (Nor-EVs) can improve LVEF (WMD: 9.07, 95% CI: 6.76 to 11.38, I² = 80.7%), LVFS (WMD: 3.03, 95% CI: 0.79 to 5.27, I² = 86.3%), and reduce infarct size (WMD: −12.15, 95% CI: −19.12 to −5.18, I² = 96.8%). Compared with Nor-EVs, Hypo-EVs can improve LVEF (WMD: 5.11, 95% CI: 1.63 to 8.60, I² = 95%), LVFS (WMD: 6.54, 95% CI: 4.08 to 8.99, I² = 90.6%), and reduce infarct size (WMD: −7.42, 95% CI: −12.97 to −1.87, I² = 97.2%). These results suggest that Hypo-EVs could show more improvement than Nor-EVs therapy on cardiac repair in the preclinical MI animal model. However, future well-designed large animal studies might be necessary to clarify the methods and effects of Hypo-EVs therapy to help provide new ideas for future engineered EVs design.

中文翻译：

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用于心肌梗死临床前动物模型心脏修复的低氧干细胞衍生细胞外囊泡：荟萃分析

鉴于干细胞衍生的细胞外囊泡 (EVs) 的修饰可以提高其再生效率，越来越多的研究关注干细胞衍生的细胞外囊泡 (Hypo-EVs) 在心脏修复中的低氧预处理的治疗潜力。我们的荟萃分析旨在评估 Hypo-EV 在心肌梗死 (MI) 临床前动物模型中的心脏修复。我们检索了截至 2021 年 1 月的 PubMed、EMBASE 和 Web of Science。主要结果是左心室射血分数 (LVEF)。第二个结果是左心室缩短分数（LVFS）和梗死面积。随机效应模型用于计算汇总加权平均差 (WMD) 和 95% 置信区间 (CI)。九项研究满足纳入标准。与模型组相比，I ²  = 80.7%)、LVFS (WMD: 3.03, 95% CI: 0.79 to 5.27, I ²  = 86.3%), 减少梗死面积 (WMD: -12.15, 95% CI: -19.12 to -5.18, I ²  = 96.8%）。与 Nor-EV 相比，Hypo-EV 可提高 LVEF（WMD：5.11，95% CI：1.63 至 8.60，I ²  = 95%）、LVFS（WMD：6.54，95% CI：4.08 至 8.99，I ²  = 90.6 ） %），并减少梗死面积（WMD：-7.42，95% CI：-12.97 至 -1.87，I ² = 97.2%）。这些结果表明，在临床前心肌梗死动物模型中，Hypo-EVs 比 Nor-EVs 治疗对心脏修复的改善更大。然而，未来精心设计的大型动物研究可能需要阐明 Hypo-EVs 治疗的方法和效果，以帮助为未来的工程 EVs 设计提供新思路。