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The Effect of miRNA-Modified Exosomes in Animal Models of Spinal Cord Injury: A meta-Analysis.

ABSTRACT: Background: Spinal cord injury (SCI) is currently not completely curable. Exosomes have been widely used in preclinical studies of spinal cord injury. Here, in this meta-analysis, we focused on evaluating the overall efficacy of therapies based on miRNA-modified exosomes on functional recovery in animal models of SCI. Methods: PubMed, embase and Web of Science library databases were searched. Relevant literature was included, and the random effects model was used to assess the overall effect of the intervention, with outcomes expressed as SMD. The primary outcome included motor function scores. Risk of bias (ROB) was assessed using the ROB tool of the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE). R version 4.1.1software and Review Manager software were used for meta-analysis. Results: A total of 11 preclinical studies were included. The meta-analysis revealed that miRNA-modified exosome therapy was effective in improving motor function scores compared with exosomes alone or control therapy (standardized mean difference: 4.21; 95% confidence interval: 3.39-5.04). There was significant asymmetry in the funnel plot, and trim-and-fill analysis revealed four unpublished studies of motor scores. The quality of all included studies was evaluated with SYRCLE's ROB tool. The SCI model, administration time and dose had an impact on the effect of the treatment. Conclusion: MiRNA-modified exosomes have shown great potential in the treatment of SCI. Moreover, the efficacy of miRNA-modified exosomes was superior to that of exosomes alone.

SUBMITTER: Hu M

PROVIDER: S-EPMC8770826 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundAlthough some previous studies have indicated that extracellular vesicles (EVs) secreted from miRNA-modified mesenchymal stem cells (MSCs) may be more effective as compared with control EVs in the treatment of rats with spinal cord injuries (SCI), the efficacy of this treatment modality remains controversial.ObjectivesThe current study comprehensively evaluated the efficacy of different administered doses of EVs, including miRNA-overexpressing MSCs-derived EVs, among SCI rats. The efficacy of EVs' treatment was evaluated in different SCI models to provide evidence for preclinical trials.MethodsWe extensively searched the following databases to identify relevant studies: PubMed, Embase, Scopus, The Cochrane Library, and Web of Science (from inception to July 20, 2022). Two trained investigators independently screened literature, extracted the data, and evaluated literature quality.ResultsThirteen studies were included in this network meta-analysis. The results demonstrated that miRNA-overexpressing MSCs-derived EVs (100 and 200 μg of total protein of EVs) significantly improved hind limb motor function in rats at early stages of SCI (i.e., at 3 days after injury) as compared with EVs (100 and 200 μg of total protein of EVs, respectively). However, in the middle and late stages (14 and 28 days), there were no statistically significant differences between EVs with 200 μg dosages and miRNA-loaded EVs with 100 μg dosages. In the late stages (28 days), there were no statistically significant differences between EVs with 100 μg dosages and miRNA-loaded EVs with 200 μg dosages. We found that miRNA-overexpressing MSCs-derived EVs significantly improved motor function among early-stage SCI rats in a compression and contusion model (3 days) as compared with MSCs-derived EVs and miRNA-overexpressing MSCs-derived EVs likewise significantly improved motor function among SCI rats in a contusion model at middle and late stages (14 and 28 days).ConclusionOur results suggest that miRNA-overexpressing MSCs-derived EVs (200 μg of total protein of EVs) may be the best choice for the effective treatment of SCI, and miRNA-overexpressing MSCs-derived EVs may likewise be the best choice for treating contusions. However, there are some risks of bias in our included studies, and the mechanisms underlying the efficacy of EVs remain unclear.Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=282051, identifier: CRD42021282051.

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The Effect of miRNA-Modified Exosomes in Animal Models of Spinal Cord Injury: A meta-Analysis.

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