The therapeutic potential of extracellular vesicles in preclinical stroke models: a systematic review and meta-analysis

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Abstract

Objectives
Currently there is a paucity of clinically available regenerative therapies for stroke. Extracellular vesicles (EVs) have been investigated for their potential as modulators of regeneration in the post-stroke brain. This systematic review and meta-analysis aims to provide a summary of the efficacy of therapeutic EVs in preclinical stroke models, to inform future research in this emerging field.
Methods
Studies were identified by a comprehensive literature search of two online sources and subsequent screening. Studies utilising lesion volume or neurological score as outcome measures were included. Standardised mean difference (SMD) and 95% confidence intervals were calculated using a restricted maximum-likelihood random effects model. Publication bias was assessed with Egger’s regression and presented as funnel plots with trim and fill analysis. Subgroup analysis was performed to assess effects of different study variables. Study quality and risk of bias were assessed using the CAMARADES checklist.
Results
A total of 20 publications were included in the systematic review, of which 19 were assessed in the meta-analysis (43 comparisons). Overall, EV interventions improved lesion volume (SMD: -1.95, 95% CI: -2.72, -1.18) and neurological scores (SMD:-1.26, 95% CI: -1.64, -0.87) compared to control groups. Funnel plots were asymmetrical suggesting publication bias, and trim and fill analysis predicted 7 missing studies for lesion volume. Subgroup analysis suggested administration at 0-23 hours post-stroke was the most effective timepoint for EV treatment. The median score on the CAMARADES checklist was 7 (IQR: 5-8).
Conclusions
EVs may offer a promising new avenue for stroke therapies, as EV-based interventions had positive impacts on lesion volume and neurological score in preclinical stroke models.

Bibliographical metadata

Original languageEnglish
JournalBMJ Open Science
Early online date24 Feb 2020
DOIs
Publication statusE-pub ahead of print - 24 Feb 2020