Introduction: Traumatic brain injury (TBI) is a major global health issue, with approximately 27 million new cases annually. Common causes include falls, motor vehicle accidents, and assaults. TBI significantly increases the risk of developing post-traumatic epilepsy (PTE), which may emerge weeks to years after the initial injury. Currently, effective therapies for both TBI and PTE remain limited. Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) have demonstrated anti-inflammatory and neuroprotective effects in preclinical TBI models. VivaZome’s proprietary cells (VZT-PCs) share characteristics with MSCs, including similar surface markers and immunomodulatory properties. Native EVs from VZT-PCs are enriched in microRNAs with known anti-inflammatory potential. This study assessed the therapeutic effect of VZT-PC-derived EVs in a murine model of TBI.
Methods: Adult C57BL/6 mice underwent controlled cortical impact and received either vehicle or VZT-PC-EVs (2.19 × 10¹⁰ particles, i.v.). Functional recovery was assessed using behavioural tests, and PTE was evaluated using pentylenetetrazol (PTZ) challenge and video-EEG.
Results and Conclusions: Native EV-treated TBI mice showed significantly improved performance in rotarod trials, indicating enhanced motor coordination. Exploratory behaviour in the elevated plus maze was also improved. While spatial learning deficits in the Barnes maze persisted, EV-treated mice exhibited a trend toward reduced seizure frequency and increased latency to generalized seizures, though not statistically significant. Biodistribution analysis confirmed EV presence in the brain 3 hours post-injection, suggesting their ability to reach injured regions. These findings support the therapeutic potential of VZT-PC-derived native EVs in enhancing motor function and possibly reducing epileptogenicity following TBI, highlighting VZT-PCs as a promising source of EVs for brain injury therapy.