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bioRxiv · 10.64898/2026.08.20.745982

Regenerative Neural Stem Cell Therapy Improves Multidomain Neurological Deficits after Traumatic Brain Injury in Nonhuman Primates

Arredendo, M.·Daadi, E. W.·Daadi, E. S.·Oh, T.·Karam, J.·Sadighian, H.·Nishi, R. A.·Cummings, B. J.·Daadi, M. M.
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Abstract

Traumatic brain injury (TBI) produces persistent multidomain disability spanning motor, cognitive, emotional and sleep-wake function, with no approved restorative therapy. Here, we tested pd.S6.133.hNSC, a cryopreserved, GMP-like human neural stem cell (hNSC) product derived from Shef-6 and FACS-sorted on CD133+/CD34-, in a randomized dose-ranging study in common marmosets subjected to controlled cortical impact (n = 18). Seven weeks after injury, animals received MRI-guided stereotactic transplantation into perilesional cortex bilaterally under tacrolimus immunosuppression, with either vehicle or pd.S6.133.hNSC at 1 million (1e6) or 5 million (5e6) cell dose. At 3 months post-transplantation, 5e6 dosage improved executive and problem-solving performances (Object Retrieval Task with Barrier Detour), gait dynamics (CatWalk assay), anxiety-like behavior (Human Intruder Test), and actigraphy-derived sleep-wake and circadian rhythm measures relative to vehicle and 1e6 dose. Longitudinal 7T MRI demonstrated a dose-dependent reduction in lesion volume and preservation of corpus callosum white matter volume in the 5e6 group. Transplantation was well tolerated, with no observed adverse events across 1,197 cumulative post-transplant animal-days. Histopathology at 3 months post-transplantation in NHPs showed engraftment without tumor formation or abnormal tissue overgrowth. These findings support the safety and multidomain efficacy of a cryopreserved hNSC product in a nonhuman primate TBI model and inform translational development toward first-in-human testing with clinically aligned endpoints.

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Arredendo, M., Daadi, E. W., Daadi, E. S., Oh, T., Karam, J., Sadighian, H., Nishi, R. A., Cummings, B. J., Daadi, M. M.. 2026-08-24. Regenerative Neural Stem Cell Therapy Improves Multidomain Neurological Deficits after Traumatic Brain Injury in Nonhuman Primates. https://doi.org/10.64898/2026.08.20.745982

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