2. Academic Validation
  3. Human induced pluripotent stem cell-derived inner ear organoids reveal hair cell damage and plasticity after cisplatin and gentamicin exposure

Human induced pluripotent stem cell-derived inner ear organoids reveal hair cell damage and plasticity after cisplatin and gentamicin exposure

  • Dis Model Mech. 2026 Jun 1;19(6):dmm052511. doi: 10.1242/dmm.052511.
Amy W A Lucassen 1 2,  Winnie M C van den Boogaard 1 2,  Esther Fousert 1 2,  Jingyuan Zhang 3 4 5,  Karl R Koehler 3 6 4 5,  John C M J de Groot 1,  Peter Paul G van Benthem 1,  Wouter H van der Valk 1 2,  Heiko Locher 1 2
Affiliations

Affiliations

  • 1 OtoBiology Leiden, Department of Otorhinolaryngology and Head and Neck Surgery, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
  • 2 The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
  • 3 Department of Otolaryngology, Boston Children's Hospital, Boston, MA 02115, USA.
  • 4 F.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, MA 02115, USA.
  • 5 Department of Otolaryngology-Head and Neck Surgery, Harvard Medical School, Boston, MA 02115, USA.
  • 6 Department of Plastic and Oral Surgery, Boston Children's Hospital, Boston, MA 02115, USA.
PMID: 41773293 DOI: 10.1242/dmm.052511
Abstract

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.

Keywords

Cisplatin; Gentamicin; Human induced pluripotent stem cells; Inner ear; Organoids; Ototoxicity.

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