Native and Bioengineered Exosomes for Ischemic Stroke Therapy

Abstract

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.

Bone Marrow Mesenchymal Stem Cell-Derived Exosomes Accelerate Functional Recovery After Spinal Cord Injury by Promoting the Phagocytosis of Macrophages to Clean Myelin Debris

“…These unique features make exosomes promising nanometer platforms or carriers for drug delivery ( He et al, 2018 ; Kalluri and LeBleu, 2020 ; Hade et al, 2021 ; Samal et al, 2021 ). However, in vivo administration of unmodified exosomes demonstrated limited targeting ability, and the exosomes were normally trapped in nonspecific organs, such as the liver, spleen, kidney, and lung, and they showed rapid clearance from the blood circulation after systemic injection ( Hade et al, 2021 ; Khan et al, 2021 ). To improve the targeting of exosomes and overcome the limitations of the systemic injection of exosomes, exosomes could be genetically modified, and direct targeting of inflated macrophages in the injured spinal cord should be considered.…”

The Genetic Basis of Strokes in Pediatric Populations and Insight into New Therapeutic Options

“…Previously, it was stated that miR-124 has proneuronal activities for both the developing and mature brain. Exosomes containing miR-124, through the processes of cortical neurogenesis, promote cortical neural progenitors to achieve neuronal identity and confer recovery after ischemia [182]. The exosomes produced by endothelial progenitor cells (EPCs) contain high amounts of miRNA-126 and miRNA-296, and have an effect of promoting angiogenesis and anti-apoptosis [183].…”

Extracellular vesicles in atherothrombosis and cardiovascular disease: Friends and foes

“…Their pathological effect may be essentially detrimental, as for instance, in subjects with a myocardial infarction, coronary flow reserve was inversely associated with platelet-and endothelial-derived circulating MV carrying proatherogenic proteins [105]. Oppositely, a large body of evidence suggests that exosomes, at least externally administered, might exert a protective effect in ischemic events [106][107][108]. In an experimental model of stroke, rats were administered exosomes derived from bone marrow mesenchymal stem cells, 2 h after middle cerebral artery occlusion.…”