Human induced pluripotent stem cell-derived MGE cell grafting after status epilepticus attenuates chronic epilepsy and comorbidities via synaptic integration
Abstract
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Dec 17, 2018
- Source ID
- 10.1073/pnas.1814185115
Entities
People
- Adrian Bates
- Ashok K. Shetty
- Bharathi Hattiangady
- Bing Shuai
- Darwin J. Prockop
- Dinesh Upadhya
- Maheedhar Kodali
- Olagide W. Castro
- Sahithi Attaluri
- Su-chun Zhang
- Yi Dong
Organizations
- National Institutes of Health
- Texas Emerging Technology Fund
- United States Department of Defense
- United States Department of Veterans Affairs
- University of Wisconsin–Madison