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A stumbling block in treating GABAergic interneuron dysfunction in acquired temporal lobe epilepsy (TLE) has been the incapacity of the adult human brain to replace interneurons through adult neurogenesis. Recent advances in the field of stem cell biology led to the development of pluripotent stem cells (iPSCs), and this technology has been used in combination with effective differentiation protocols for generating GABAergic neurons from human iPSCs. Neuroscientists have now established that transplanting human iPSC-derived GABAergic interneurons into the hippocampus in rodent models of TLE can suppress spontaneous recurrent seizures. Basic research studies in mice further showed that interneuron transplants prevent some of the neuropathological hallmarks of TLE that contribute to hyperexcitability and epileptogenesis by forming new inhibitory synaptic connections within the host hippocampus and preventing neuropathological changes from developing. These basic scientific findings paved the way for a recent clinical trial testing human neuron transplantation in patients with severe TLE that is having promising early results.<\/jats:p>","DOI":"10.1177\/15357597251318571","type":"journal-article","created":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T11:50:59Z","timestamp":1742385059000},"page":"179-183","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":7,"title":["From Stumbling Blocks to Stepping Stones: Progress in Treating Temporal Lobe Epilepsy With Stem Cell Transplantation"],"prefix":"10.1177","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5151-0543","authenticated-orcid":false,"given":"Janice R.","family":"Naegele","sequence":"first","affiliation":[{"name":"Wesleyan University"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,3,19]]},"reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2022-330979"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2023.106045"},{"key":"e_1_3_2_4_2","volume-title":"Cold Spring Harb Perspect Med","author":"Pitkanen A","year":"2015","unstructured":"Pitkanen A, Lukasiuk K, Dudek FE, et al. 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