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Human iPSC Derived GABA Ergic Precursor Cell Therapy for Chronic Epilepsy

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Technical Report,30 Sep 2015,29 Sep 2016

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Texas A and M University System College Station United States

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The goal of this project is to examine whether grafting of human medial ganglionic eminence hMGE-like precursor cells generated from the human induced pluripotent stem cells hiPSCs into the hippocampus of chronically epileptic ratsCERs would 1 diminish the frequency and intensity of spontaneous recurrent seizures SRS, Specific Aim 1, SA1and 2 ameliorate learning and memory impairments and depression Specific Aim 2, SA2. Studies performed so far have focused on rigorously addressing the seizure-modulating effects of grafts in SA1. Three weeks of continuous EEG recordings have been collected and compared between the four groups of epileptic rats CERs receiving hMGE-like cell grafts and cyclosporine an immunosuppressant to promote the survival of human cell grafts in the rat brain, CERs receiving sham-grafting surgery, CERs receiving cyclosporine only and CERs receiving no treatment. The results showed that, in comparison to all three control CER groups, CERs receiving hMGE-like cell grafts displayed 75-78 reduction in the frequency of all SRS, 77-80 reduction in the frequency stage V seizures and 71-75 reduction in the total time spent in seizure activity. Notably, the robust suppression of seizures was associated with an excellent yield, pervasive migration and robust differentiation 70 of graft-derived cells into gamma-amino butyric acid positive GABA-ergic interneurons in the hippocampus. Thus, hMGE-like cell grafting into the hippocampus in a rat model of temporal lobe epilepsy greatly suppresses seizures with the addition of a large number of new GABA-ergic interneurons.

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