2026/03/03 by Amy W. A. Lucassen, Winnie M.C. van den Boogaard, Esther Fousert +6 · 1 voice
Medicine · Neuroscience · #Cisplatin #Cochlea #Gentamicin #Hair cell #Hearing, Cochlea, Tinnitus, Genetics #Induced pluripotent stem cell #Inner ear #Organ of Corti #Organoid #Ototoxicity #Vestibular and auditory disorders #Voice and Speech Disorders
paper · doi:10.1242/dmm.052511
openalex publication_date 2026/03/03 · openalex created_date 2026/03/04 · openalex updated_date 2026/08/01
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.