ArticleInternational journal of molecular sciences2021
Human Stem Cell-Derived GABAergic Interneurons Establish Efferent Synapses onto Host Neurons in Rat Epileptic Hippocampus and Inhibit Spontaneous Recurrent Seizures.
Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 29 citations in OpenAlex.
- Stem cell-based therapeutics in epilepsy: current advances and future prospects.Stem cells translational medicine · 2026Review
- Human stem cell-derived neurons establish functional inhibitory-excitatory cortical circuits in a chimeric transplantation model.Scientific reports · 2026Article
- Advancements in Stem Cell Therapy for Managing Drug-Resistant Epilepsy.Molecular neurobiology · 2026Review
- Chemogenetics with PSAMGene therapy · 2025Article
- Review
- Cell therapy for neurological disorders.Nature medicine · 2024Review
- Article
- 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
- Stem Cell Transplantation Represents a New Strategy for the Treatment of Epilepsy.Neuroscience bulletin · 2024Article
- Viral encephalitis and seizures cause rapid depletion of neuronal progenitor cells and alter neurogenesis in the adult mouse dentate gyrus.Frontiers in cellular neuroscience · 2024Article
- Human pallial MGE-type GABAergic interneuron cell therapy for chronic focal epilepsy.Cell stem cell · 2023Article
- Molecular and Cellular Mechanisms of Epilepsy.International journal of molecular sciences · 2023Article
- hUMSC vs. hUMSC-Exosome: Which One Is Better for Epilepsy?Pharmaceuticals (Basel, Switzerland) · 2022Review
- Regulation of Inhibitory Signaling at the Receptor and Cellular Level; Advances in Our Understanding of GABAergic Neurotransmission and the Mechanisms by Which It Is Disrupted in Epilepsy.Frontiers in synaptic neuroscience · 2022Review
- Stem Cell Therapy in Treating Epilepsy.Frontiers in neuroscience · 2022Review
- Rewiring the seizing brain: stem cell grafts as neuromodulatory architects in epilepsy therapy.Frontiers in neurologyReview
- Stem Cells: Recent Developments Redefining Epilepsy Therapy.Cell transplantationReview
Corrections and comments
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Authors and funding
7 authors at 1 institution in 2 countries.
Funding
Abstract
Epilepsy is a complex disorder affecting the central nervous system and is characterised by spontaneously recurring seizures (SRSs). Epileptic patients undergo symptomatic pharmacological treatments, however, in 30% of cases, they are ineffective, mostly in patients with temporal lobe epilepsy. Therefore, there is a need for developing novel treatment strategies. Transplantation of cells releasing γ-aminobutyric acid (GABA) could be used to counteract the imbalance between excitation and inhibition within epileptic neuronal networks. We generated GABAergic interneuron precursors from human embryonic stem cells (hESCs) and grafted them in the hippocampi of rats developing chronic SRSs after kainic acid-induced status epilepticus. Using whole-cell patch-clamp recordings, we characterised the maturation of the grafted cells into functional GABAergic interneurons in the host brain, and we confirmed the presence of functional inhibitory synaptic connections from grafted cells onto the host neurons. Moreover, optogenetic stimulation of grafted hESC-derived interneurons reduced the rate of epileptiform discharges in vitro. We also observed decreased SRS frequency and total time spent in SRSs in these animals in vivo as compared to non-grafted controls. These data represent a proof-of-concept that hESC-derived GABAergic neurons can exert a therapeutic effect on epileptic animals presumably through establishing inhibitory synapses with host neurons.
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Registered trials
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