Preclinical development of a neural stem cell therapy for stroke and traumatic brain injury
Baker, Emily Wyatt
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Stroke and traumatic brain injury (TBI) are leading causes of death and long-term disability worldwide. Despite the socioeconomic burden of these neural injuries, there are no restorative therapies. Induced pluripotent stem cell-derived neural stem cells (iNSCs) may be the critically needed therapy to restore neurological function after brain injury. Preclinical studies demonstrate that iNSCs are a multimodal therapeutic that improves recovery after neural injury. However, the enthusiasm of these results has been stifled by the hundreds of therapeutics shown to be effective in preclinical neural injury models but have failed in clinical trials, thus suggesting a lack of translatability of preclinical animal models to human patients. Compared to the rodent, the sole preclinical model iNSC therapy has been tested in, the pig possesses striking similarities in brain anatomy and physiology compared to the human and may be an ideal animal model to bridge the gap between preclinical rodent models and human patients. However, injury models and outcome measures are not well characterized in the pig, and more studies in the pig are needed to determine if large animals truly carry greater predictive power of clinical efficacy. The objectives of these studies were to 1) develop a translational pig model to study TBI pathophysiology and recovery mechanisms, and 2) assess whether iNSC therapy improves recovery in a pig stroke model. These studies strengthen current preclinical therapeutic development strategies for neural injury by improving the translational capacity of animal models and provide further insight into the potential of iNSC therapy for human patients.