期刊
BRAIN AND BEHAVIOR
卷 8, 期 5, 页码 -出版社
WILEY
DOI: 10.1002/brb3.972
关键词
functional outcome scale; induced pluripotent stem cell; large animal stroke model; neural progenitor cell; porcine stroke model
资金
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke [R01NS093314]
- University of Georgia Office of the Vice President for Research
Introduction: Stroke is the leading cause of disability in the United States but current therapies are limited with no regenerative potential. Previous translational failures have highlighted the need for large animal models of ischemic stroke and for improved assessments of functional outcomes. The aims of this study were first, to create a post-stroke functional outcome assessment scale in a porcine model of middle cerebral artery occlusion (MCAO) and second, to use this scale to determine the effect of human-induced-pluripotent-cell-derived neural progenitor cells (iNPCs) on functional outcome in this large animal stroke model. Materials and Methods: Eight 6-month-old Landrace mix pigs underwent permanent MCAO. Five days following MCAO, pigs received intraparenchymal injections of either iNPCs or PBS. A post-stroke assessment scale was developed to measure functional outcome. Evaluations were performed at least 1-3 days prior to MCAO and repeated 1 day, 3 days, and 5 days post-stroke as well as 1 day, 3 days, 1 week, 2 weeks, 4 weeks, 6 weeks, 9 weeks, and 12 weeks post-injection. Comparisons of scores between animals receiving iNPCs or PBS only were compared using a two-way ANOVA and a Tukey's post-hoc t test. Results: The developed scale was able to consistently determine differences between healthy and stroked pigs at all time points. iNPC-treated pigs showed a significantly faster recovery in their overall scores relative to PBS-only treated pigs with the parameters of appetite and body posture exhibiting the most improvement in the iNPC-treated group. Conclusions: We developed a robust and repeatable functional assessment tool that can reliably detect stroke and recovery, while also showing for the first time that iNPC therapy leads to functional recovery in a translational pig ischemic stroke model. These promising results suggest that iNPCs may 1day serve as a first in class cell therapeutic for ischemic stroke.
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