Neuroprotection from Stem Cell-Derived Human Adipose Extracellular Vesicles Intranasally Administered 24 Hours After Stroke in Rats. 

Abstract

Ischemic stroke is a major cause of death and disability, demanding innovative and accessible therapeutic strategies. Approaches presenting an optimal period for therapeutic intervention and new treatment administration routes are promising tools for stroke treatment. We evaluated the potential neuroprotective properties of nasally administered human adipose tissue stem cells (hAT-MSCs)-derived extracellular vesicles (EVs) obtained from healthy individuals who underwent liposuction. A single intranasal EV (200 µg/kg) was administered 24 h after a focal permanent ischemic stroke in rats. A higher tropism of EVs was observed in the peri-infarct zone surrounding the infarct core. In the same brain region, there was a significant decrease in the infarct volume, improvement of the blood-brain barrier, and re-stabilization of vascularization. In addition, EVs recovered the impairment of long-term motor and behavioral performance induced by an ischemic stroke. Surprisingly, one single intranasal EVs administration reestablished: i) front paws symmetry, ii) short- and long-term memory, and iii) anxiety-like behavior. In line with the findings, our work highlights hAT-MSC-derived EVs as a promising therapeutic strategy for stroke.

Intranasal Delivery of Mesenchymal Stem Cells-Derived Extracellular Vesicles for the Treatment of Neurological Diseases

“…A single intranasal administration of MSC‐derived EVs, 24 hours after a focal permanent ischemic stroke in rats, was enough to significantly reduce the infarct volume, improve the integrity of the blood‐brain barrier, and restabilize vascularization. In addition, the treatment restored the long‐term motor and behavioral performance that had been impaired by the stroke 107 . The mechanism is thought to be by preventing secretion of proinflammatory cytokines and inducing anti‐inflammatory factors, inhibiting apoptosis of cells after injury, and promoting angiogenesis and cell regeneration.…”