Abstract TP141: Mesenchymal Stem Cell Derived Exosomes as a Modulator of Neuroinflammation Following Cortical Injury

Abstract

In this study, we tested Mesenchymal Stem Cell derived exosomes as a therapeutic to enhance recovery in our established nonhuman primate model of cortical injury. After pretraining monkeys on fine motor hand task,10 aged female monkeys were randomly assigned to an exosome treatment group (n=5) or a vehicle control (PBS) group (n=5). Then, in a single surgery, monkeys received a lesion in the hand representation of M1. One day and 14 days after injury, monkeys were given 4x10 11 exosomes/kg or PBS intravenously. Fifteen days after surgery, motor assessments were resumed for 12 weeks. The five treated monkeys all returned to pre-operative latencies to retrieve on motor tasks while none of the control monkeys returned to pre-operative latencies. To assess recovery mechanisms, cerebrospinal fluid (CSF) collected across the post-injury recovery period and terminal brain tissue were analyzed for markers of neuroinflammation. Preliminary ELISA results in both groups showed a trend towards increased Myelin Basic Protein (MBP) in CSF 24 hours after cortical injury followed by a gradual decline over 6 weeks. Interestingly, MBP levels declined more rapidly in exosome-treated animals, suggesting a potential reduction in damage. Scholl analysis of microglia branching in perilesional grey matter showed that exosomes increased ramification length, branching complexity, and convex hull 3D coverage volume. These findings suggest an increase in the surveying capacity of microglia in treated monkeys that may serve to promote repair after injury. Further, optical density analyses of microglial markers revealed a lower expression in treated monkeys of IBA1/P2RY12 and the MHCII antigen-presenting marker, LN3. This is consistent with decreased microglial activation associated with exosome treatment. These results provide evidence for the translational potential of exosomes as a treatment for human stroke.