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Exosomes are natural cells-derived vesicles, which are at the forefront toward clinical success for various diseases, including cerebral ischemia. Exosomes mediate cell-to-cell communication in different brain cells during both physiological and pathological conditions. Exosomes are an extensively studied type of extracellular vesicle, which are considered to be the best alternative for stem cell–based therapy. They can be secreted by various cell types and have unique biological properties. Even though native exosomes have potential for ischemic stroke therapy, some undesirable features prevent their success in clinical applications, including a short half-life, poor targeting property, low concentration at the target site, rapid clearance from the lesion region, and inefficient payload. In this review, we highlight exosome trafficking and cellular uptake and survey the latest discoveries in the context of exosome research as the best fit for brain targeting owing to its natural brain-homing abilities. Furthermore, we overview the methods by which researchers have bioengineered exosomes (BioEng-Exo) for stroke therapy. Finally, we summarize studies in which exosomes were bioengineered by a third party for stroke recovery. This review provides up-to-date knowledge about the versatile nature of exosomes with a special focus on BioEng-Exo for ischemic stroke. Standard exosome bioengineering techniques are mandatory for the future and will lead exosomes toward clinical success for stroke therapy.

Native and Bioengineered Exosomes for Ischemic Stroke Therapy