Treating neurological disorders is a challenging obstacle due to multifactorial and complex etiologies. The therapeutic benefits of intranasal administration of extracellular vesicles isolated from mesenchymal stem cells have gained much attention in recent years. Extracellular vesicles retain their parental cells advantages. Intranasal administration of extracellular vesical provides a noninvasive method to bypass the blood-brain barrier and target specific pathological regions. In the present study, the authors summarize the current research of mesenchymal stem cells-derived extracellular vesicles administrated by nasal pathways and their potential as a promising therapeutic approach.
There have been multiple reports over the last decade of improvements in various rodent models of neurodegenerative diseases or acute brain insults, following the transplantation of mesenchymal stromal cells (MSCs).1–3 MSCs are multipotent adult stromal cells (https://www.sciencedirect.com/topics/immunology-and-microbiology/adult-stem-cell), which can be isolated from bone marrow (BM), umbilical cord (UC) (https://www.sciencedirect.com/topics/immunology-and-microbiology/umbilical-cord), placental, deciduous teeth, or adipose tissue (AT) (https://www.sciencedirect.com/topics/immunology-and-microbiology/adipose-tissue). They have the potential to differentiate into osteoblasts, chondrocytes (https://www.sciencedirect.com/topics/immunology-and-microbiology/chondrocyte), and adipocytes, as well as other cell types.4 The understanding of mechanisms by which MSC exert their clinical effects is evolving and involves both paracrine and direct phagocyte activation.5
Cumulative data from recent research have indicated that relatively few MSCs engraft at sites of injury when administered intravenously (IV), because they are trapped in the capillaries of the lungs and rapidly cleared from the body. Of these, a minor fraction acquire certain phenotypic characteristics of neurons, although they do not fully differentiate to generate functional neurons within a brain lesion.6–8 While MSCs are rapidly cleared from the body, their therapeutic benefits are typically preserved far longer, indicating that the effects are mediated by the cellular secretome, and specifically by small extracellular vesicles (EVs).9,10 These small EVs are nanovesicles (30-150 nm) formed within multivesicular bodies in the endosomal system, or by shedding from the plasma membrane. They are released by a variety of cells, can pass the blood-brain barrier (BBB),11 and are known mediators of intercellular communication. Accumulated evidence from recent years indicates that MSC-derived EVs may serve as a promising therapy for neurological disorders as a result of their ability to regulate neuroprotection, induce neurogenesis, modulate inflammation, and degrade misfolded protein aggregates.12–14 They owe these extensive capabilities to their diverse cargo that may comprise a wide variety of nucleic acids, proteins, and lipids. These constituents reflect the characteristics of the cells from which the EVs are derived, and can modulate gene expression in recipient cells upon fusion with the plasma membrane.
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