Abstract
Mesenchymal stem cells have previously been shown to mediate brain repair after stroke; they secrete 50–100 nm complexes called extracellular vesicles (EVs), which could be responsible for provoking neurovascular repair and functional recovery. EVs have been observed by electron microscopy and NanoSight, and they contain associated proteins such as CD81 and Alix. This purified, homogeneous population of EVs was administered intravenously after subcortical stroke in rats. To evaluate the EVs effects, we studied the biodistribution, proteomics analysis, functional evaluation, lesion size, fiber tract integrity, axonal sprouting and white matter repair markers. We found that a single administration of EVs improved functional recovery, fiber tract integrity, axonal sprouting and white matter repair markers in an experimental animal model of subcortical stroke. EVs were found in the animals’ brain and peripheral organs after euthanasia. White matter integrity was in part restored by EVs administration mediated by molecular repair factors implicated in axonal sprouting, tract connectivity, remyelination and oligodendrogenesis. These findings are associated with improved functional recovery. This novel role for EVs presents a new perspective in the development of biologics for brain repair.
Highlights
Extracellular vesicles (EVs) are small heterogeneous microvesicles, 30 to 100 nm in diameter, that store within themselves multivesicular bodies (DNA, RNA, proteins and lipids) and information on their various biological functions and their cell type-specific molecular composition
We aimed to investigate whether intravenous administration of MSC-derived extracellular vesicles (EVs) could induce functional recovery, promote oligodendrogenesis and aid white matter fiber repair when axonal tract integrity has been compromised, to potentially serve as a brain repair therapy after an experimental animal model of subcortical stroke
We found co-labeling between DiI-labeled EVs with VEGF, NeuN, CNP-ase and Iba-1 at 24 hours after EVs administration (Fig. 1F and G)
Summary
Extracellular vesicles (EVs) are small heterogeneous microvesicles, 30 to 100 nm in diameter, that store within themselves multivesicular bodies (DNA, RNA, proteins and lipids) and information on their various biological functions and their cell type-specific molecular composition. They are widely distributed in serum, urine, saliva and other biological fluids. We aimed to investigate whether intravenous administration of MSC-derived EVs could induce functional recovery, promote oligodendrogenesis and aid white matter fiber repair when axonal tract integrity has been compromised, to potentially serve as a brain repair therapy after an experimental animal model of subcortical stroke
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