Abstract DP348: Combination Endovascular Mesenchymal and Neural Stem Cell Therapy in a Rodent Model of Ischemic Stroke

Introduction: Recombinant tPA and mechanical thrombectomy reduce ischemic stroke damage, yet many patients are still left with significant disability. Due to their anti-inflammatory and repair effects, therapy with Mesenchymal stem cells (MSCs) have shown promise in AIS models and even in small early clinical trials. However, their capacity for direct neural regeneration is limited. Neural stem cells (NSCs), with their regenerative ability and smaller size, offer the potential for better reach to the ischemic site and promote repair. Past studies are limited to studying these key candidate cell types individually, especially via traditional injection routes which do not ensure adequate cell distribution around ischemic area. Hypothesis: We hypothesized that intra-arterial (IA) delivery of a combination of MSCs and NSCs has synergistic benefits in mitigating functional deficits and neural tissue loss. Methods: In male Sprague Dawley (SD) rats with reversible Middle Cerebral artery occlusion (MCAo) we administered IA NSCs and MSCs and compared it to IA MSCs alone at 24h post reperfusion. Our previous studies with IA 1x10⁵ MSCs in MCAo stroke conferred efficacy and was found to be the maximally tolerated dose (MTD). Further, our recent dose escalation study with IA NSCs indicated that 5x10⁵ cells is safe and effective, offering significant functional benefits. We performed a comprehensive serial assessment of endpoints for 1 week, using behavior analyses, infarct volume, and neuronal cell count and compared to Brains were collected post transcardial perfusion (PFA) for immunohistology analysis. Results: As compared to PBS control/IA MSCs alone, the combination IA therapy, 24 h post reperfusion showed and significantly superior neuronal deficit scoring (NDS) which encompasses visual perception, postural reflex, sensorimotor integration, proprioception as well as infarct volume reduction, and neuronal survival especially at the day 6 post-stroke (p<0. 05). Histological assessment of inflammation and regenerative markers is underway. Conclusion: IA NSC and MSC combination therapy proved to be safe with superior efficacy compared to IA MSCs alone. This study provides a foundation for further optimization of IA NSC and MSC combination therapy envisioning complementary therapeutic benefits.