Xu Kangli, Zhao Xiaohui, He Yuxuan, Guo Hongxin, Zhang Yunke
The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China.
The First Clinical Medical College of Henan University of Chinese Medicine, Zhengzhou, China.
Front Pharmacol. 2024 Oct 23;15:1481617. doi: 10.3389/fphar.2024.1481617. eCollection 2024.
We aimed to evaluate the efficacy of stem cell-derived exosomes for treating ischemic stroke and to screen for the optimal administration strategy.
We searched PubMed, Web of Science, Embase, Cochrane Library, and Scopus databases for relevant studies published from their inception to 31 December 2023. Conventional and network meta-analyses of the routes of administration, types, and immune compatibility of stem cell-derived exosomes were performed using the cerebral infarct volume (%) and modified neurological severity score (mNSS) as outcome indicators.
A total of 38 randomized controlled animal experiments were included. Conventional meta-analysis showed that compared with the negative control group: intravenous administration significantly reduced the cerebral infarct volume (%) and mNSS; intranasal administration significantly reduced the cerebral infarct volume (%); and intracerebral administration significantly reduced the mNSS. Adipose-derived mesenchymal stem cell-derived exosomes (ADSC-Exos), bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exos), dental pulp stem cell-derived exosomes (DPSC-Exos) and neural stem cell-derived exosomes (NSC-Exos) significantly reduced the cerebral infarct volume (%) and mNSS; Endothelial progenitor cell-derived exosomes (EPC-Exos), embryonic stem cell-derived exosomes (ESC-Exos), induced pluripotent stem cell-derived exosomes (iPSC-Exos) and neural progenitor cell-derived exosomes (NPC-Exos) significantly reduced the cerebral infarct volume (%); Umbilical cord mesenchymal stem cell-derived exosomes (UCMSC-Exos) significantly reduced the mNSS; and there was no significant difference between urogenital stem cell-derived exosomes (USC-Exos) and negative controls. Engineered modified exosomes had better efficacy than unmodified exosomes. Both allogeneic and xenogeneic stem cell-derived exosomes significantly reduced the cerebral infarct volume (%) and the mNSS. The network meta-analysis showed that intravenous administration was the best route of administration for reducing the cerebral infarct volume (%) and mNSS. Among the 10 types of stem cell-derived exosomes that were administered intravenously, BMSC-Exos were the best type for reducing the cerebral infarct volume (%) and the mNSS. Allogeneic exosomes had the best efficacy in reducing the cerebral infarct volume (%), whereas xenogeneic stem cell-derived exosomes had the best efficacy in reducing the mNSS.
This meta-analysis, by integrating the available evidence, revealed that intravenous administration is the best route of administration, that BMSC-Exos are the best exosome type, that allogeneic exosomes have the best efficacy in reducing the cerebral infarct volume (%), and that xenogeneic exosomes have the best efficacy in reducing mNSS, which can provide options for preclinical studies. In the future, more high-quality randomized controlled animal experiments, especially direct comparative evidence, are needed to determine the optimal administration strategy for stem cell-derived exosomes for ischemic stroke.
https://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42024497333, PROSPERO, CRD42024497333.
我们旨在评估干细胞衍生外泌体治疗缺血性中风的疗效，并筛选最佳给药策略。
我们检索了PubMed、Web of Science、Embase、Cochrane图书馆和Scopus数据库，以获取从建库至2023年12月31日发表的相关研究。以脑梗死体积（%）和改良神经功能缺损评分（mNSS）作为结局指标，对干细胞衍生外泌体的给药途径、类型和免疫相容性进行传统荟萃分析和网状荟萃分析。
共纳入38项随机对照动物实验。传统荟萃分析表明，与阴性对照组相比：静脉注射显著降低脑梗死体积（%）和mNSS；鼻内给药显著降低脑梗死体积（%）；脑内给药显著降低mNSS。脂肪间充质干细胞衍生外泌体（ADSC-Exos）、骨髓间充质干细胞衍生外泌体（BMSC-Exos）、牙髓干细胞衍生外泌体（DPSC-Exos）和神经干细胞衍生外泌体（NSC-Exos）显著降低脑梗死体积（%）和mNSS；内皮祖细胞衍生外泌体（EPC-Exos）、胚胎干细胞衍生外泌体（ESC-Exos）、诱导多能干细胞衍生外泌体（iPSC-Exos）和神经祖细胞衍生外泌体（NPC-Exos）显著降低脑梗死体积（%）；脐带间充质干细胞衍生外泌体（UCMSC-Exos）显著降低mNSS；泌尿生殖干细胞衍生外泌体（USC-Exos）与阴性对照组之间无显著差异。工程改造的外泌体比未改造的外泌体疗效更好。同种异体和异种干细胞衍生外泌体均显著降低脑梗死体积（%）和mNSS。网状荟萃分析表明，静脉注射是降低脑梗死体积（%）和mNSS的最佳给药途径。在静脉注射的10种干细胞衍生外泌体中，BMSC-Exos是降低脑梗死体积（%）和mNSS的最佳类型。同种异体外泌体在降低脑梗死体积（%）方面疗效最佳，而异种干细胞衍生外泌体在降低mNSS方面疗效最佳。
本荟萃分析通过整合现有证据表明，静脉注射是最佳给药途径，BMSC-Exos是最佳外泌体类型，同种异体外泌体在降低脑梗死体积（%）方面疗效最佳，异种外泌体在降低mNSS方面疗效最佳，这可为临床前研究提供选择。未来，需要更多高质量的随机对照动物实验，尤其是直接比较证据，以确定干细胞衍生外泌体治疗缺血性中风的最佳给药策略。
https://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42024497333，PROSPERO，CRD42024497333。
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