Abstract WP366: Dose-Response Evaluation of Intra-Arterial Neural Stem Cell Therapy in Acute Ischemic Stroke Model

Introduction: Preclinical studies in the past two decades have shown promise in cell therapies for stroke. Intra-arterial (IA) delivery of stem cells is minimally invasive and uses similar techniques to endovascular thrombectomy making it attractive for clinical translation. Recent studies from our lab have shown the safety and efficacy of IA-Mesenchymal Stem Cells (MSC) treatment in rodent and canine ischemic stroke models primarily through anti-inflammatory mechanisms. However, there are sparse studies of IA neural stem cells (NSCs), which may have direct impact on neuronal survival and regeneration. Methods: In this study we tested three different doses (1 x 10 5 , 5 x 10 5 , 1 x 10 6 ) of IA NSCs and compared their efficacy with PBS control and intra-arterial MSC groups in a rat model of reversible middle cerebral artery occlusion (rMCAO). Stem cell therapy was administered 24 hours after reperfusion. Behavioral and functional improvements, as well as postmortem histology were performed to evaluate the efficacy of different doses. Results: Our findings showed significant improvements in stroke volume, surviving neurons, neurological deficit scoring, and other functional behavioral tests for the 5 x 10 5 NSC group at 7 days after stroke. Additionally, neurological deficit scoring showed significant improvements at the higher dose of 1 x 10 6 NSC as well. Significantly elevated expression of NeuN, Sox2, and Nestin markers were also detected in the ipsilateral dentate gyrus at 7 days after stroke in the 5 x 10 5 NSCs dose group. Conclusions: These novel findings help us evaluate safe and optimally effective dose for IA-NSC in ischemic stroke post-reperfusion. They form the basis for developing future pre-clinical studies and designing a successful clinical translation of this novel approach.