{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T19:43:53Z","timestamp":1792266233242,"version":"4.4.0"},"reference-count":89,"publisher":"The Company of Biologists","issue":"6","license":[{"start":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T00:00:00Z","timestamp":1772496000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Fonden","doi-asserted-by":"crossref","award":["NNF21CC0073729"],"award-info":[{"award-number":["NNF21CC0073729"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100005039","name":"Leids Universitair Medisch Centrum","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100005039","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Ototoxicity is a leading cause of sensory deficits, including hearing loss and balance disorders. Predicting ototoxicity is challenging owing to translatability issues of animal models and limited access to human inner ear tissue. Known ototoxic drugs, such as cisplatin (a chemotherapeutic) and gentamicin (an aminoglycoside antibiotic), cause irreversible damage to sensory hair cells and neurons. Here, we establish human induced pluripotent stem cell (hiPSC)-derived inner ear organoids as an in vitro model for studying ototoxicity. Exposure to cisplatin and gentamicin led to hair cell and neuronal loss, disrupted organoid architecture and increased cell damage, including apoptosis, in a dose-dependent manner. Remarkably, prolonged culture of treated organoids showed re-emergence of otic vesicle structures with sensory hair cells and neurons. SOX10+ otic epithelial cells exhibited increased Ki-67 expression, indicating a potential for developmental plasticity. Our findings demonstrate the value of hiPSC-derived inner ear organoids as a platform for human ototoxicity modeling and provide a basis for testing otoprotective interventions, offering insights into the intrinsic plasticity of developing inner ear cells.<\/jats:p>","DOI":"10.1242\/dmm.052511","type":"journal-article","created":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T07:57:00Z","timestamp":1772524620000},"source":"Crossref","is-referenced-by-count":5,"title":["Human induced pluripotent stem cell-derived inner ear organoids reveal hair cell damage and plasticity after cisplatin and gentamicin exposure"],"prefix":"10.1242","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4003-928X","authenticated-orcid":false,"given":"Amy W. A.","family":"Lucassen","sequence":"first","affiliation":[{"name":"Leiden University Medical Center 1 OtoBiology Leiden, Department of Otorhinolaryngology and Head and Neck Surgery , , 2333 ZA Leiden ,","place":["The Netherlands"]},{"name":"The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Leiden University Medical Center 2 , 2333 ZA Leiden ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5712-3990","authenticated-orcid":false,"given":"Winnie M. C.","family":"van den Boogaard","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center 1 OtoBiology Leiden, Department of Otorhinolaryngology and Head and Neck Surgery , , 2333 ZA Leiden ,","place":["The Netherlands"]},{"name":"The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Leiden University Medical Center 2 , 2333 ZA Leiden ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0792-3364","authenticated-orcid":false,"given":"Esther","family":"Fousert","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center 1 OtoBiology Leiden, Department of Otorhinolaryngology and Head and Neck Surgery , , 2333 ZA Leiden ,","place":["The Netherlands"]},{"name":"The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Leiden University Medical Center 2 , 2333 ZA Leiden ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7968-629X","authenticated-orcid":false,"given":"Jingyuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Boston Children's Hospital 3 Department of Otolaryngology , , Boston, MA 02115 ,","place":["USA"]},{"name":"F.M. Kirby Neurobiology Center, Boston Children's Hospital 5 , Boston, MA 02115 ,","place":["USA"]},{"name":"Harvard Medical School 6 Department of Otolaryngology-Head and Neck Surgery , , Boston, MA 02115 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0685-538X","authenticated-orcid":false,"given":"Karl R.","family":"Koehler","sequence":"additional","affiliation":[{"name":"Boston Children's Hospital 3 Department of Otolaryngology , , Boston, MA 02115 ,","place":["USA"]},{"name":"Boston Children's Hospital 4 Department of Plastic and Oral Surgery , , Boston, MA 02115 ,","place":["USA"]},{"name":"F.M. Kirby Neurobiology Center, Boston Children's Hospital 5 , Boston, MA 02115 ,","place":["USA"]},{"name":"Harvard Medical School 6 Department of Otolaryngology-Head and Neck Surgery , , Boston, MA 02115 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C. M. J.","family":"de Groot","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center 1 OtoBiology Leiden, Department of Otorhinolaryngology and Head and Neck Surgery , , 2333 ZA Leiden ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7946-1912","authenticated-orcid":false,"given":"Peter Paul G.","family":"van Benthem","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center 1 OtoBiology Leiden, Department of Otorhinolaryngology and Head and Neck Surgery , , 2333 ZA Leiden ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5661-7796","authenticated-orcid":false,"given":"Wouter H.","family":"van der Valk","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center 1 OtoBiology Leiden, Department of Otorhinolaryngology and Head and Neck Surgery , , 2333 ZA Leiden ,","place":["The Netherlands"]},{"name":"The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Leiden University Medical Center 2 , 2333 ZA Leiden ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4174-0270","authenticated-orcid":false,"given":"Heiko","family":"Locher","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center 1 OtoBiology Leiden, Department of Otorhinolaryngology and Head and Neck Surgery , , 2333 ZA Leiden ,","place":["The Netherlands"]},{"name":"The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Leiden University Medical Center 2 , 2333 ZA Leiden ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2026,3,3]]},"reference":[{"key":"2026030302565708000_DMM052511C1","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1038\/s41419-020-2551-8","article-title":"Cisplatin-induced ototoxicity in organotypic cochlear cultures occurs independent of gap junctional intercellular communication","volume":"11","author":"Abitbol","year":"2020","journal-title":"Cell Death Dis."},{"key":"2026030302565708000_DMM052511C2","doi-asserted-by":"publisher","first-page":"15790","DOI":"10.3390\/ijms232415790","article-title":"Pericytes of Stria Vascularis are targets of cisplatin-induced ototoxicity: new insights into the molecular mechanisms involved in blood-labyrinth barrier breakdown","volume":"23","author":"Anfuso","year":"2022","journal-title":"Int. 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