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Mesenchymal Stem Cell-Extracellular Vesicle Therapy in Patients with Stroke

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Abstract

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.

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Abbreviations

BBB:

Blood–brain barrier

CDN:

Cell-derived nanovesicles

ECM:

Extracellular matrix

EGF:

Epidermal growth factor

ESCs:

Embryonic stem cells

EVs:

Extracellular vesicles

FDA:

Food and Drug Administration

FGF:

Fibroblast growth factor

GMP:

Good Manufacturing Practice

iPSCs:

Induced pluripotent stem cells

ISEV:

International Society for Extracellular Vesicles

lncRNAs:

Long noncoding RNAs

MiRNA:

MmicroRNAs

MISEV:

Minimal Information for Studies of Extracellular Vesicles

MRI:

Magnetic resonance imaging

MSC:

Mesenchymal stem cells

NSCs:

Neural stem cells

PDGF:

Platelet-derived growth factor

PEG:

Polyethylene glycol

VEGF:

Vascular endothelial growth factor

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Bang, O.Y., Kim, E.H., Moon, G.J., Cha, J.M. (2022). Mesenchymal Stem Cell-Extracellular Vesicle Therapy in Patients with Stroke. In: Haider, K.H. (eds) Handbook of Stem Cell Therapy. Springer, Singapore. https://doi.org/10.1007/978-981-16-6016-0_45-1

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