Ischemic stroke is a prominent cause of death and disability, demanding innovative therapeutic strategies. Accordingly, extracellular vesicles (EVs) released from mesenchymal stem cells are promising tools for stroke treatment. In this study, we evaluated the potential neuroprotective properties of EVs released from human adipose tissue stem cells (hAT-MSC), which were obtained from a healthy individual submitted to liposuction. A single intranasal EVs administration was performed 24 h after the ischemic stroke in rats. The EVs brain penetration and the tropism to brain zone of ischemia was observed 18 h after administration. Thus, we measured EVs neuroprotection against the ischemic stroke-induced impairment on long-term motor and behavioral performance. Indeed, one single intranasal EVs administration reversed the stroke damages on: i) front paws symmetry; ii) working memory, short- and long-term memory; iii) anxiety-like behavior. These findings highlight hAT-MSC-derived EVs as a promising therapeutic strategy in stroke.

Ischemic stroke is a prominent cause of death and disability, demanding for innovative and reachable therapeutic strategies. Thus, approaches presenting optimal period for therapeutic intervention and new routes of treatments administration as promising tools for stroke treatment. In this study, we evaluated the potential neuroprotective properties of nasally administration of human adipose tissue stem cells (hAT-MSC)-derived extracellular vesicles (EVs), obtained from healthy individuals submitted to liposuction. A single intranasal EVs (200 µg/Kg) administration performed 24 h after a focal permanent ischemic stroke in rats. Was observed a higher tropism of EVs by peri-infarct zone, surrounding the infarct core. Interestingly, in the same brain region, was observed a significant decrease in the volume of the infarct, improvement the blood-brain barrier and re-stabilization of vascularization. In addition, EVs recover the impairment on long-term motor and behavioral performance induced by ischemic stroke. Surprisingly, one single intranasal EVs administration reestablished: i) front paws symmetry; ii), short- and long-term memory; iii) anxiety-like behavior. In keeping with this, our work highlights hAT-MSC-derived EVs as a promising therapeutic strategy in stroke.