hPSC-Derived Maturing GABAergic Interneurons Ameliorate Seizures and Abnormal Behavior in Epileptic Mice
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Seizure disorders debilitate more than 65,000,000 people worldwide, with temporal lobe epilepsy (TLE) being the most common form. Previous studies have shown that transplantation of GABA-releasing cells results in suppression of seizures in epileptic mice. Derivation of interneurons from human pluripotent stem cells (hPSCs) has been reported, pointing to clinical translation of quality-controlled human cell sources that can enhance inhibitory drive and restore host circuitry. In this study, we demonstrate that hPSC-derived maturing GABAergic interneurons (mGINs) migrate extensively and integrate into dysfunctional circuitry of the epileptic mouse brain. Using optogenetic approaches, we find that grafted mGINs generate inhibitory postsynaptic responses in host hippocampal neurons. Importantly, even before acquiring full electrophysiological maturation, grafted neurons were capable of suppressing seizures and ameliorating behavioral abnormalities such as cognitive deficits, aggressiveness, and hyperactivity. These results provide support for the potential of hPSC-derived mGIN for restorative cell therapy for epilepsy.
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Human cortical interneurons have been shown to integrate extensively into the host mouse brain thanks to the remarkable migratory properties of this class of neurons.
“Human cortical interneurons have been shown to integrate extensively into the host mouse brain thanks to the remarkable migratory properties of this class of neurons”
From Xenotransplanted human cortical neurons reveal species-specific development and functional integration into mouse visual circuits (2019) · cites this paper as Cunningham et al., 2014
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- Authors
- Cunningham, M., Cho, J.-H., Leung, A., Savvidis, G., Ahn, S., Moon, M., Lee, P. K. J., Han, J. J., Azimi, N., Kim, K.-S., Bolshakov, V. Y., & Chung, S.
- Affiliations
- Harvard University (US)
- Corresponding author
- Chung, Sangmi
- ORCID
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2014-11
- Volume
- 15
- Issue
- 5
- Pages
- 559-573
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- PMC
- PMC4270101
- OpenAlex
- W2027310774
- Cited by
- 218
- References
- 47
- Citations by year
- 2026: 9 · 2025: 11 · 2024: 22 · 2023: 14 · 2022: 18 · 2021: 10 · 2020: 24 · 2019: 19 · 2018: 22 · 2017: 20 · 2016: 27 · 2015: 21 · 2014: 1
- FWCI
- 17.56
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell stem cell (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health
- Harvard Stem Cell Institute
- National Institute of Mental Health (R01MH090464, MH090464)
- National Institute of Neurological Disorders and Stroke (R01NS070577, NS079977, NS070577, R21NS079977)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- human pluripotent stem cells, GABAergic interneurons, temporal lobe epilepsy, cell transplantation, cell therapy, seizure suppression, interneuron migration, hippocampus, optogenetics, cognitive impairment, aggression, hyperactivity
- MeSH terms
- Animals, Behavior, Animal, Cell Differentiation, Cell Movement, Female, Hippocampus, Humans, Interneurons, Male, Median Eminence, Neural Inhibition, Seizures, Mice, SCID, Mice, Inbred NOD, Stem Cell Transplantation, Pluripotent Stem Cells, Synaptic Potentials, GABAergic Neurons, Optogenetics
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