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骨髓间充质干细胞衍生外泌体修复脊髓损伤:基于大鼠模型的系统评价和荟萃分析

Repair of spinal cord injury by bone marrow mesenchymal stem cell-derived exosomes: a systematic review and meta-analysis based on rat models.

作者信息

Ye Zhongduo, Zheng Yukun, Li Ningning, Zhang Huaibin, Li Qiangqiang, Wang Xiong

机构信息

The First Hospital of Lanzhou University, Lanzhou, China.

The First Clinical Medical College of Lanzhou University, Lanzhou, China.

出版信息

Front Mol Neurosci. 2024 Aug 7;17:1448777. doi: 10.3389/fnmol.2024.1448777. eCollection 2024.

Abstract

OBJECTIVE

This study aims to systematically evaluate the efficacy of bone marrow mesenchymal stem cell-derived exosomes (BMSCs-Exo) in improving spinal cord injury (SCI) to mitigate the risk of translational discrepancies from animal experiments to clinical applications.

METHODS

We conducted a comprehensive literature search up to March 2024 using PubMed, Embase, Web of Science, and Scopus databases. Two researchers independently screened the literature, extracted data, and assessed the quality of the studies. Data analysis was performed using STATA16 software.

RESULTS

A total of 30 studies were included. The results indicated that BMSCs-Exo significantly improved the BBB score in SCI rats (WMD = 3.47, 95% CI [3.31, 3.63]), inhibited the expression of the pro-inflammatory cytokine TNF- (SMD = -3.12, 95% CI [-3.57, -2.67]), and promoted the expression of anti-inflammatory cytokines IL-10 (SMD = 2.76, 95% CI [1.88, 3.63]) and TGF- (SMD = 3.89, 95% CI [3.02, 4.76]). Additionally, BMSCs-Exo significantly reduced apoptosis levels (SMD = -4.52, 95% CI [-5.14, -3.89]), promoted the expression of axonal regeneration markers NeuN cells/field (SMD = 3.54, 95% CI [2.65, 4.42]), NF200 (SMD = 4.88, 95% CI [3.70, 6.05]), and the number of Nissl bodies (SMD = 1.89, 95% CI [1.13, 2.65]), and decreased the expression of astrogliosis marker GFAP (SMD = -5.15, 95% CI [-6.47, -3.82]). The heterogeneity among studies was primarily due to variations in BMSCs-Exo transplantation doses, with efficacy increasing with higher doses.

CONCLUSION

BMSCs-Exo significantly improved motor function in SCI rats by modulating inflammatory responses, reducing apoptosis, inhibiting astrogliosis, and promoting axonal regeneration. However, the presence of selection, performance, and detection biases in current animal experiments may undermine the quality of evidence in this study.

摘要

目的

本研究旨在系统评价骨髓间充质干细胞来源的外泌体(BMSCs-Exo)在改善脊髓损伤(SCI)方面的疗效,以降低从动物实验到临床应用过程中出现转化差异的风险。

方法

我们使用PubMed、Embase、Web of Science和Scopus数据库进行了全面的文献检索,检索截至2024年3月。两名研究人员独立筛选文献、提取数据并评估研究质量。使用STATA16软件进行数据分析。

结果

共纳入30项研究。结果表明,BMSCs-Exo显著提高了SCI大鼠的BBB评分(加权均数差[WMD]=3.47,95%置信区间[CI][3.31, 3.63]),抑制了促炎细胞因子TNF-的表达(标准化均数差[SMD]=-3.12,95% CI[-3.57, -2.67]),并促进了抗炎细胞因子IL-10(SMD=2.76,95% CI[1.88, 3.63])和TGF-(SMD=3.89,95% CI[3.02, 4.76])的表达。此外,BMSCs-Exo显著降低了细胞凋亡水平(SMD=-4.52,95% CI[-5.14, -3.89]),促进了轴突再生标志物NeuN细胞/视野(SMD=3.54,95% CI[2.65, 4.42])、NF200(SMD=4.88,95% CI[3.70, 6.05])的表达以及尼氏小体数量(SMD=1.89,95% CI[1.13, 2.65]),并降低了星形胶质细胞增生标志物GFAP的表达(SMD=-5.15,95% CI[-6.47, -3.82])。研究之间的异质性主要归因于BMSCs-Exo移植剂量的差异,剂量越高疗效越好。

结论

BMSCs-Exo通过调节炎症反应、减少细胞凋亡、抑制星形胶质细胞增生和促进轴突再生,显著改善了SCI大鼠的运动功能。然而,当前动物实验中存在的选择、实施和检测偏倚可能会削弱本研究证据的质量。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/559e/11335736/c5dfc3a12a4b/fnmol-17-1448777-g001.jpg

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