Cell Stem Cell
Volume 15, Issue 5, 6 November 2014, Pages 559-573
Journal home page for Cell Stem Cell

Article
hPSC-Derived Maturing GABAergic Interneurons Ameliorate Seizures and Abnormal Behavior in Epileptic Mice

https://doi.org/10.1016/j.stem.2014.10.006Get rights and content
Under an Elsevier user license
open archive

Highlights

  • Human-PSC-derived mGINs engraft within mouse epileptic brain

  • Human mGINs migrate extensively and integrate within host epileptic circuitry

  • The activation of human mGINs induces inhibitory synaptic responses in host neurons

  • mGIN grafts suppress seizure and abnormal behavior

Summary

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.

Cited by (0)

6

Co-first author

7

Present Address: Department of Cell Biology and Neuroscience, University of California, Riverside, Riverside, CA 92521, USA