Human induced pluripotent stem cell-derived MGE cell grafting after status epilepticus attenuates chronic epilepsy and comorbidities via synaptic integration

TLDR

The antiepileptogenic effects included reduced host interneuron loss, abnormal neurogenesis, and mossy fiber sprouting, while antiepileptic effects were indicated by increased seizures after silencing graft‑derived interneurons. Autologous cell therapy avoids immune suppression and promotes durable graft–host integration. Human iPSC‑derived MGE cell grafting into the hippocampus after status epilepticus markedly reduces chronic spontaneous seizures through antiepileptogenic and antiepileptic mechanisms, improves cognitive and mood function, and supports its application for temporal lobe epilepsy.

Abstract

Significance This study provides evidence that human induced pluripotent stem cell (hiPSC)-derived medial ganglionic eminence (MGE) cell grafting into the hippocampus after status epilepticus can greatly reduce the frequency of spontaneous seizures in the chronic phase through both antiepileptogenic and antiepileptic effects. The antiepileptogenic changes comprised reductions in host interneuron loss, abnormal neurogenesis, and aberrant mossy fiber sprouting, whereas the antiepileptic effects were evident from an increased occurrence of seizures after silencing of graft-derived interneurons. Additional curative impacts of grafting comprised improved cognitive and mood function. The results support the application of autologous human MGE cell therapy for temporal lobe epilepsy. Autologous cell therapy is advantageous as such a paradigm can avoid immune suppression and promote enduring graft–host integration.