Human iPSC Derived GABA Ergic Precursor Cell Therapy for Chronic Epilepsy
Abstract
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 rats(CERs) would: (1) diminish the frequency and intensity of spontaneous recurrent seizures (SRS, Specific Aim 1, SA1);and (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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2016
- Accession Number
- AD1025938
Entities
People
- Ashok K. Shetty
Organizations
- Texas A&M University