ArticleProceedings of the National Academy of Sciences of the United States of America2019
Human induced pluripotent stem cell-derived MGE cell grafting after status epilepticus attenuates chronic epilepsy and comorbidities via synaptic integration.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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Who cites it
79 citing papers in PubMed, 126 citations in OpenAlex.
- Reverse bioengineering of the liver: developmental principles for next-generation liver-on-a-chip systems.Communications biology · 2026Review
- Stem cell-based therapeutics in epilepsy: current advances and future prospects.Stem cells translational medicine · 2026Review
- Epilepsy: Molecular Pathogenesis and Emerging Therapies.MedComm · 2026Review
- Human iPSC-derived GABAergic interneuron transplantation restores circuit balance and cognitive function in an Alzheimer's disease model.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
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- Transplantation of GABAergic Interneuron Progenitors Restores Cortical Circuit Function in an Alzheimer's Disease Mouse Model.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Adult hippocampal neurogenesis: New avenues for treatment of brain disorders.Stem cell reports · 2025Review
- Three-dimensional co-culturing reveals human stem cell-derived somatostatin interneurons with subclass expression.Stem cell reports · 2025Article
- Chemogenetics with PSAMGene therapy · 2025Article
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- Parvalbumin interneurons: the dark and bright sides of a key playmaker of neural circuits and behavior.Frontiers in cellular neuroscience · 2025Review
- Electroacupuncture Preconditioning Ameliorates the Ischemic Microenvironment to Improve Long-Term Potentiation in Chronic Cerebral Hypoperfusion Rats With MGE Neural Progenitor Transplantation.Neural plasticity · 2025Article
- Extracellular vesicles from human-induced pluripotent stem cell-derived neural stem cells alleviate proinflammatory cascades within disease-associated microglia in Alzheimer's disease.Journal of extracellular vesicles · 2024Article
- Overcoming Graft Rejection in Induced Pluripotent Stem Cell-Derived Inhibitory Interneurons for Drug-Resistant Epilepsy.Brain sciences · 2024Review
- Cell therapy for neurological disorders.Nature medicine · 2024Review
- Microglia in Microbiota-Gut-Brain Axis: A Hub in Epilepsy.Molecular neurobiology · 2024Review
- FDA-approved cannabidiol [EpidiolexMilitary Medical Research · 2024Article
- Aberrant adult neurogenesis in intractable epilepsy: can GABAergic progenitor transplantation normalize this process?Neural regeneration research · 2024Article
- In and out: Benchmarking in vitro, in vivo, ex vivo, and xenografting approaches for an integrative brain disease modeling pipeline.Stem cell reports · 2024Review
- Updated Toolbox for Assessing Neuronal Network Reconstruction after Cell Therapy.Bioengineering (Basel, Switzerland) · 2024Review
19 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
Abstract
Medial ganglionic eminence (MGE)-like interneuron precursors derived from human induced pluripotent stem cells (hiPSCs) are ideal for developing patient-specific cell therapy in temporal lobe epilepsy (TLE). However, their efficacy for alleviating spontaneous recurrent seizures (SRS) or cognitive, memory, and mood impairments has never been tested in models of TLE. Through comprehensive video- electroencephalographic recordings and a battery of behavioral tests in a rat model, we demonstrate that grafting of hiPSC-derived MGE-like interneuron precursors into the hippocampus after status epilepticus (SE) greatly restrained SRS and alleviated cognitive, memory, and mood dysfunction in the chronic phase of TLE. Graft-derived cells survived well, extensively migrated into different subfields of the hippocampus, and differentiated into distinct subclasses of inhibitory interneurons expressing various calcium-binding proteins and neuropeptides. Moreover, grafting of hiPSC-MGE cells after SE mediated several neuroprotective and antiepileptogenic effects in the host hippocampus, as evidenced by reductions in host interneuron loss, abnormal neurogenesis, and aberrant mossy fiber sprouting in the dentate gyrus (DG). Furthermore, axons from graft-derived interneurons made synapses on the dendrites of host excitatory neurons in the DG and the CA1 subfield of the hippocampus, implying an excellent graft-host synaptic integration. Remarkably, seizure-suppressing effects of grafts were significantly reduced when the activity of graft-derived interneurons was silenced by a designer drug while using donor hiPSC-MGE cells expressing designer receptors exclusively activated by designer drugs (DREADDs). These results implied the direct involvement of graft-derived interneurons in seizure control likely through enhanced inhibitory synaptic transmission. Collectively, the results support a patient-specific MGE cell grafting approach for treating TLE.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.