Abstract
Aim:Human stem cell-derived extracellular vesicles (EV) provide many advantages over cell-based therapies for the treatment of functionally compromised tissue beds and organ sites. Here we aimed to highlight multiple administration routes for the potential treatment of various forms of brain injury.Methods:Human neural stem cell-derived EV were isolated from conditioned media and administered via three distinct routes: intrahippocampal transplantation, retro-orbital vein injection, and intranasal. EV were administered after which brains were evaluated to determine the capability of EV to translocate into normal tissue.Results:Data showed no significant differences in the amount of EV able to translocate across the brain, indicating the functional equivalence of each administration route to effectively deliver EV to the brain parenchyma.Conclusion:Findings show that both systemic administration routes (retro-orbital vein or intranasal delivery) afforded effective penetrance and perfusion of EV throughout the brain in a minimally invasive manner, and point to a translationally tractable option for treating certain neurological disorders including those resulting from cranial irradiation procedures.
Highlights
Extracellular vesicles (EV) are secreted by nearly every mammalian cell type and contain a wealth of bioactive cargo capable of modulating target cell function through a variety of paracrine signaling www.jcmtjournal.comIoannides et al
Cranial irradiation was associated with significant behavioral deficits that were ameliorated by EV treatments
EV derived from a single batch were administered to mice via IC, RO, and IN routes, after which distinct brain regions (PFC, subventricular zone (SVZ), dentate gyrus (DG)) were imaged 2 days following treatments to assess brain penetrance of EV delivered through each route
Summary
Depending on such factors as cellular origin, cargo contents, membrane composition, and target cell indications, interactions of EV with damaged, diseased, or otherwise compromised tissue beds can promote functional recovery[1,2]. Exosomes are smaller (30-100 nm) intraluminal vesicles within endosome-derived multivesicular bodies that fuse with and release from the plasma membrane[4]. For the resolution of radiation injury, no clear evidence has demonstrated a therapeutic advantage of human stem cell-derived MV over exosomes or vice versa, so the EV-based treatments used in this study include the full-size range of vesicles secreted into the conditioned medium by the proliferating human neural stem cells
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