基于临床前动物模型的随机对照试验的荟萃分析：干细胞来源的外泌体治疗急性心肌梗死。
Stem cell-derived exosomes in the treatment of acute myocardial infarction in preclinical animal models: a meta-analysis of randomized controlled trials.
机构信息
Department of Cardiology, The Second Affiliated Hospital of Fujian Medical University, No. 34 North Zhongshan Road, Quanzhou, 362000, Fujian Province, China.
Department of Neurosurgery, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian Province, China.
出版信息
Stem Cell Res Ther. 2022 Apr 8;13(1):151. doi: 10.1186/s13287-022-02833-z.
BACKGROUND
Exosomes (EXOs) derived from stem cells have become a potential new treatment for acute myocardial infarction (AMI). However, their impact is still not fully understood. Therefore, we performed this meta-analysis to systematically review the efficacy of EXOs on AMI in preclinical animal models.
METHODS
We searched PubMed, EMBASE, and the Web of Science from September 1, 1980 to September 1, 2021, to retrieve the studies reporting the therapeutic effects of EXOs on AMI animal models. Secondary endpoints include the fractional shortening (FS), infarct size (IS), fibrosis area (FA), the TNF-α, IL-6 and IL-10 levels, the apoptosis rate and the number of autophagic vesicles. Two authors independently screened the articles based on inclusion and exclusion criteria. All statistical analyses were conducted using Stata14.0.
RESULTS
Ten studies satisfied the inclusion criteria. Pooled analyses demonstrated that the levels of LVEF (WMD = 3.67%; 95% CI 2.28-5.07%; P = 0.000), FS (WMD = 3.69%; 95% CI 2.06-5.33%; P = 0.000), IS (WMD = -4.52%, 95% CI - 7.14 to - 1.9%; P = 0.001), and FA (WMD = -7.04%, 95% CI - 8.74 to - 5.34%; P = 0.000), TNF-α (WMD = -3.09, 95% CI - 5.47 to - 0.72; P = 0.011), TL-6 (WMD = -6.34, 95% CI - 11.2 to - 1.49; P < 0.01), TL-10 (WMD = 6.37, 95% CI 1.53-11.21; P = 0.01), the apoptosis rate (WMD = -8.23, 95% CI - 15.29 to - 1.17; P = 0.000), and the number of autophagic vesicles (WMD = -4.52, 95% CI - 7.43 to - 1.62; P = 0.000). Subgroup analysis showed that the EXOs were derived from HMSCs. Subgroup analysis showed that the EXOs derived from HMSCs, and that exosome therapy immediately after myocardial infarction can better improve the LVEF.
CONCLUSIONS
EXOs therapy has the potential to improve cardiac function, fibrogenesis, and inflammatory response, as well as reducing cell apoptosis and autophagy in preclinical AMI animal models. This can inform future human clinical trials of EXOs.
背景
来源于干细胞的外泌体（EXOs）已成为治疗急性心肌梗死（AMI）的一种有潜力的新方法。然而，其影响仍未被完全了解。因此，我们进行了这项荟萃分析，以系统地回顾 EXOs 在 AMI 动物模型中的疗效。
方法
我们从 1980 年 9 月 1 日至 2021 年 9 月 1 日，在 PubMed、EMBASE 和 Web of Science 上检索了报道 EXOs 对 AMI 动物模型治疗效果的研究。次要终点包括分数缩短率（FS）、梗死面积（IS）、纤维化面积（FA）、TNF-α、IL-6 和 IL-10 水平、细胞凋亡率和自噬囊泡数量。两名作者根据纳入和排除标准独立筛选文章。所有统计分析均使用 Stata14.0 进行。
结果
有 10 项研究符合纳入标准。汇总分析表明，左心室射血分数（LVEF）（WMD = 3.67%；95% CI 2.28-5.07%；P = 0.000）、FS（WMD = 3.69%；95% CI 2.06-5.33%；P = 0.000）、IS（WMD = -4.52%，95% CI -7.14 至 -1.9%；P = 0.001）和 FA（WMD = -7.04%，95% CI -8.74 至 -5.34%；P = 0.000）、TNF-α（WMD = -3.09，95% CI -5.47 至 -0.72；P = 0.011）、IL-6（WMD = -6.34，95% CI -11.2 至 -1.49；P < 0.01）、IL-10（WMD = 6.37，95% CI 1.53-11.21；P = 0.01）、细胞凋亡率（WMD = -8.23，95% CI -15.29 至 -1.17；P = 0.000）和自噬囊泡数量（WMD = -4.52，95% CI -7.43 至 -1.62；P = 0.000）。亚组分析表明，EXOs 来源于 HMSCs。亚组分析表明，来源于 HMSCs 的 EXOs，以及在心肌梗死后立即进行 EXO 治疗，可以更好地改善 LVEF。
结论
EXOs 治疗有潜力改善心肌梗死动物模型的心脏功能、纤维化和炎症反应，并减少细胞凋亡和自噬。这可以为未来的 EXOs 人类临床试验提供信息。
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