Abstract
Introduction: Pre-clinical studies have shown great promise in the use of cell-based therapies for stroke. Intra-arterial (IA) delivery directs the cells to the injured brain, is minimally invasive and widely available, making it attractive for clinical translation. Our group and others have shown the safety and efficacy of IA Mesenchymal Stem Cell (MSC) treatment in a rodent stroke model at 24 hours post-reperfusion. The optimal timing of a single dose of IA MSC is unknown. Also, whether an additional dose will lead to greater benefit and the optimal timing of the second dose need to be determined for successful translation of IA MSC to clinic. The objective of this study is to determine if dual dose IA-MSC treatment is superior to single dose and find the optimal timing for the second dose. Methods: We used a reversible middle cerebral artery occlusion (rMCAO) model for stroke in rats. IA-MSCs were administered using a PE-10 catheter at 1, 2 and 4 day after stroke as single dose. Based on the results of the first experiment, dual doses were given at 1-4, 1-6 and 1-15 day. Behavioral analysis of rotarod, neurological deficit scoring and stroke volume were determined at 30 days after treatment. Results: Single dose IA-MSC at 1day was superior (p=0.02, 0.01, 0.04) to single dose given on day 2 and no benefit was seen when given on day 4. Among the dual dose groups, 1-6 day after stroke showed significant improvement in neurodeficit score and stroke volume (p=0.007, p=0.03). However, the percentage increase in improvement in 1-6day (dual) was much higher than that observed in 1day (single) group (Fig 1). Detailed results will be presented at the meeting. Conclusion: The results of our study indicate that 1day after stroke is optimal for single dose of IA-MSC. An additional dose at 6days after stroke enhances the effect of IA-MSC in aiding symptomatic recovery and stroke lesion reduction. In summary, our findings contribute to understanding of the benefit of dual dose of IA MSC for translation to the clinic.
