{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T21:09:09Z","timestamp":1771708149311,"version":"3.50.1"},"reference-count":77,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,10,16]],"date-time":"2024-10-16T00:00:00Z","timestamp":1729036800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Background: Cell-based therapies for drug-resistant epilepsy using induced pluripotent stem cell-derived inhibitory interneurons are now in early-phase clinical trials, building on findings from trials in Parkinson\u2019s disease (PD) and Huntington\u2019s disease (HD). Graft rejection and the need for immunosuppressive therapy post-transplantation pose potential barriers to more epilepsy patients becoming potential candidates for inhibitory interneurons transplantation surgery. Objectives: The present literature review weighs the evidence for and against human leukocyte antigen (HLA)-mediated graft rejection in PD and HD and examines the potential advantages and drawbacks to five broad approaches to cell-based therapies, including autologous cell culture and transplantation, in vivo reprogramming of glial cells using viral vectors, allogeneic transplantation using off-the-shelf cell lines, transplantation using inhibitory interneurons cultured from HLA-matched cell lines, and the use of hypoimmunogenic-induced pluripotent stem cell-derived inhibitory interneurons. The impact of surgical technique and associated needle trauma on graft rejection is also discussed. Methods: Non-systematic literature review. Results: While cell-based therapies have enjoyed early successes in treating a host of central nervous system disorders, the immunologic reaction against surgical procedures and implanted materials has remained a major obstacle. Conclusions: Adapting cell-based therapies using iPSC-derived inhibitory interneurons for epilepsy surgery will similarly require surmounting the challenge of immunogenicity.<\/jats:p>","DOI":"10.3390\/brainsci14101027","type":"journal-article","created":{"date-parts":[[2024,10,16]],"date-time":"2024-10-16T11:28:51Z","timestamp":1729078131000},"page":"1027","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Overcoming Graft Rejection in Induced Pluripotent Stem Cell-Derived Inhibitory Interneurons for Drug-Resistant Epilepsy"],"prefix":"10.3390","volume":"14","author":[{"given":"Cameron P.","family":"Beaudreault","sequence":"first","affiliation":[{"name":"School of Medicine, New York Medical College, Valhalla, NY 10595, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1915-8249","authenticated-orcid":false,"given":"Richard","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Medicine, New York Medical College, Valhalla, NY 10595, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3764-4163","authenticated-orcid":false,"given":"Carrie Rebecca","family":"Muh","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Westchester Medical Center, Valhalla, NY 10595, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashley","family":"Rosenberg","sequence":"additional","affiliation":[{"name":"School of Medicine, New York Medical College, Valhalla, NY 10595, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abigail","family":"Funari","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, SUNY Upstate Medical Center, Syracuse, NY 13210, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patty E.","family":"McGoldrick","sequence":"additional","affiliation":[{"name":"School of Medicine, New York Medical College, Valhalla, NY 10595, USA"},{"name":"Division of Pediatric Neurology, Maria Fareri Children\u2019s Hospital, Valhalla, NY 10595, USA"},{"name":"Division of Pediatric Neurology, Boston Children\u2019s Health Physicians, Hawthorne, NY 10532, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7602-3474","authenticated-orcid":false,"given":"Steven M.","family":"Wolf","sequence":"additional","affiliation":[{"name":"School of Medicine, New York Medical College, Valhalla, NY 10595, USA"},{"name":"Division of Pediatric Neurology, Maria Fareri Children\u2019s Hospital, Valhalla, NY 10595, USA"},{"name":"Division of Pediatric Neurology, Boston Children\u2019s Health Physicians, Hawthorne, NY 10532, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6236-1190","authenticated-orcid":false,"given":"Ariel","family":"Sacknovitz","sequence":"additional","affiliation":[{"name":"School of Medicine, New York Medical College, Valhalla, NY 10595, USA"},{"name":"Department of Neurosurgery, Westchester Medical Center, Valhalla, NY 10595, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8737-9978","authenticated-orcid":false,"given":"Sangmi","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Anatomy, New York Medical College, Valhalla, NY 10595, USA"},{"name":"Department of Neurosurgery, Brain Health Institute, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ 08854, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1111\/j.1528-1167.2009.02397.x","article-title":"Definition of drug resistant epilepsy: Consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies","volume":"51","author":"Kwan","year":"2010","journal-title":"Epilepsia"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1542\/pir.2019-0134","article-title":"Seizures in Children","volume":"41","author":"Fine","year":"2020","journal-title":"Pediatr. 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