Therapeutic effects of glial cell-derived extracellular vesicles on ischemic stroke in rodent models: A systematic review and meta-analysis

Treating ischemic stroke (IS) presents significant challenges; however, recent advancements suggest that glial cell-derived extracellular vesicles (GD-EVs) may offer a promising therapeutic strategy. This systematic review and meta-analysis evaluated the potential benefits of GD-EVs in IS by synthesizing data from preclinical studies. The review protocol was pre-registered with PROSPERO (CRD42024541149). Comprehensive literature searches were conducted across multiple databases, including PubMed, EMBASE, Web of Science, Cochrane Library, China National Knowledge Infrastructure, VIP Database for Chinese Technical Periodicals, Wanfang Database, and SinoMed, until April 10, 2024, to identify relevant studies. Preclinical studies investigating the utilization of GD-EVs in animal models of IS were included. Study quality was assessed using the risk of bias tool from the Systematic Review Center for Laboratory Animal Experimentation. From an initial pool of 3028 studies, 11 studies met the inclusion criteria. The analysis demonstrated that GD-EVs significantly improved neurological function, as evidenced by a reduction in the modified neurological severity score (standardized mean difference [SMD]: −1.69, 95% confidence interval [CI]: −2.15 to −1.22, p < 0.00001, and I² = 0%). GD-EVs also significantly reduced infarct volume in rodent models (SMD: −4.78, 95% CI: −6.91 to −2.66, p < 0.0001, Tau² = 0.99, and I² = 42%) and decreased brain water content and the release of pro-inflammatory factors post-stroke.

The methodological rigor of the included studies indicated sufficiently high overall quality. These findings suggest that GD-EVs hold significant promise as a novel therapeutic approach for IS and warrant further preclinical investigations before translation into clinical trials.