MSC-derived-exosomes promote functional recovery in a preclinical model of stroke

Stroke is a leading cause of death and long-term disability, making it crucial to develop strategies that promote functional recovery after stroke. Several studies have demonstrated that early treatment of ischemic stroke may reduce complications, disability, and mortality in the long term. Our study aimed at evaluating: i) the impact of a non-invasive approach, specifically intranasal (IN) administration of exosomes derived from human bone marrow mesenchymal stem cells (MSC-exo) on the recovery of forelimb motor function after stroke; ii) elucidating the underlying mechanisms. We performed experiments on mice subjected to focal ischemia by photothrombosis on the caudal forelimb primary motor cortex. The treatment started 48 hours after stroke, consisting of a single dose of exosomes that was then administered twice a week for 4 consecutive weeks. Motor function was assessed by performing a battery of tests before and 48 hours after the ischemia and then subsequently every week up to end of treatment (week 4). Our results indicated that mice treated with MSC-exo showed better performance compared to vehicle treated mice starting from the second week after stroke, as revealed by highest score in the cylinder test (% touches with impaired forelimb: 53.4% vs 33.9%; MSC-exo vs. vehicle: p=0.02) and in the grid walking test (% foot faults: 10% vs. 13%; MSC-exo vs. vehicle: p=0.009). Additionally, a preliminary histopathological assessment revealed a reduced infarct size in exosomes-treated mice (infarct volume: 0.49 mm³ vs. 1.03 mm³; MSC-exo vs. vehicle: p= 0.03), suggesting a neuroreparative effect of exosomes, favoring functional recovery.