Human <scp>iNPC</scp> therapy leads to improvement in functional neurologic outcomes in a pig ischemic stroke model

<jats:title>Abstract</jats:title><jats:sec><jats:title>Introduction</jats:title><jats:p>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 (<jats:styled-content style="fixed-case">MCAO</jats:styled-content>) and second, to use this scale to determine the effect of human‐induced‐pluripotent‐cell‐derived neural progenitor cells (<jats:styled-content style="fixed-case">iNPC</jats:styled-content>s) on functional outcome in this large animal stroke model.</jats:p></jats:sec><jats:sec><jats:title>Materials and Methods</jats:title><jats:p>Eight 6‐month‐old Landrace mix pigs underwent permanent <jats:styled-content style="fixed-case">MCAO</jats:styled-content>. Five days following <jats:styled-content style="fixed-case">MCAO</jats:styled-content>, pigs received intraparenchymal injections of either <jats:styled-content style="fixed-case">iNPC</jats:styled-content>s or <jats:styled-content style="fixed-case">PBS</jats:styled-content>. A post‐stroke assessment scale was developed to measure functional outcome. Evaluations were performed at least 1–3 days prior to <jats:styled-content style="fixed-case">MCAO</jats:styled-content> 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 <jats:styled-content style="fixed-case">iNPC</jats:styled-content>s or <jats:styled-content style="fixed-case">PBS</jats:styled-content> only were compared using a two‐way <jats:styled-content style="fixed-case">ANOVA</jats:styled-content> and a Tukey's post‐hoc <jats:italic>t</jats:italic> test.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The developed scale was able to consistently determine differences between healthy and stroked pigs at all time points. <jats:styled-content style="fixed-case">iNPC</jats:styled-content>‐treated pigs showed a significantly faster recovery in their overall scores relative to <jats:styled-content style="fixed-case">PBS</jats:styled-content>‐only treated pigs with the parameters of appetite and body posture exhibiting the most improvement in the <jats:styled-content style="fixed-case">iNPC</jats:styled-content>‐treated group.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>We developed a robust and repeatable functional assessment tool that can reliably detect stroke and recovery, while also showing for the first time that <jats:styled-content style="fixed-case">iNPC</jats:styled-content> therapy leads to functional recovery in a translational pig ischemic stroke model. These promising results suggest that <jats:styled-content style="fixed-case">iNPC</jats:styled-content>s may 1 day serve as a first in class cell therapeutic for ischemic stroke.</jats:p></jats:sec>