Mesenchymal Stem Cell-Extracellular Vesicle Therapy in Patients with Stroke

Stem cell-based therapy is a promising approach for treating acute stroke patients and stroke survivors with fixed neurological deficits. Several stem cell trials conducted in stroke patients have reported inconsistent results. Stem cells such as mesenchymal stem cells (MSCs) secrete extracellular vesicles (EVs), which harbor several molecules such as proteins and microRNAs. Recently, many preclinical studies have shown that stem cell-derived EVs can be used in stroke therapy as an alternative approach to stem cell application. This study discusses the evidence regarding the effects and underlying mechanisms of EV therapy in experimental stroke and findings of the biomarker sub-study from a randomized control trial of MSCs-based therapy in stroke patients. Moreover, the advantages and disadvantages of EVs therapy are compared with those of MSC therapy for stroke. Finally, major issues in the clinical application of EV therapeutics in stroke are discussed with relevant advances for clinical-scale EV production/ enrichment, isolation/purification, and quantification/characterization. Several methods to improve the efficacy and purity of EV products have been introduced recently. This review presents the most recent advances in MSC-derived EV therapy for stroke, focusing on the application of this strategy in patients with ischemic stroke.