2. Academic Validation
  3. Establishment of a human inner ear model reveals that gentamicin C2b is substantially less ototoxic than clinical gentamicin

Establishment of a human inner ear model reveals that gentamicin C2b is substantially less ototoxic than clinical gentamicin

  • Biomed Pharmacother. 2026 Jan:194:118915. doi: 10.1016/j.biopha.2025.118915.
Minjin Jeong 1,  Hiroaki Mohri 2,  Dongjun Han 3,  Masaharu Sakagami 4,  Konstantina M Stankovic 5
Affiliations

Affiliations

  • 1 Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, 801 Welch Rd., Stanford, CA 94304, USA. Electronic address: [email protected].
  • 2 Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, 801 Welch Rd., Stanford, CA 94304, USA. Electronic address: [email protected].
  • 3 Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, 801 Welch Rd., Stanford, CA 94304, USA. Electronic address: [email protected].
  • 4 Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, 801 Welch Rd., Stanford, CA 94304, USA. Electronic address: [email protected].
  • 5 Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, 801 Welch Rd., Stanford, CA 94304, USA; Department of Neurosurgery, Stanford University School of Medicine, 300 Pasteur Dr., Stanford, CA 94304, USA; Wu Tsai Neurosciences Institute, Stanford University, 288 Campus Dr., Stanford, CA 94304, USA. Electronic address: [email protected].
PMID: 41496330 DOI: 10.1016/j.biopha.2025.118915
Abstract

Clinically used gentamicin, a widely used Aminoglycoside antibiotic, is a mixture of 5 major subtypes with potentially differential contributions to the drug's known ototoxicity. The gentamicin subtype C2b has been previously associated with reduced ototoxicity in animal models in vitro, but its effects in humans remain uncertain due to the lack of appropriate in vitro models of the human inner ear. To address this gap, we generated otic progenitor cells (OPCs) from human induced pluripotent stem cells and used transcriptomic and immunocytochemical analyses to confirm their otic lineage identity and validate their relevance as a model for ototoxicity studies. We then compared the effects of gentamicin C2b and clinical gentamicin on cell viability and cytotoxicity in human OPCs. In parallel, we examined auditory function in mice following exposure to each formulation using auditory brainstem response and distortion product otoacoustic emissions. Gentamicin C2b exposure resulted in substantially lower cytotoxicity-via reduced mitochondria-dependent apoptosis-and higher cell viability in human OPCs, as well as dramatically attenuated hearing loss across all frequencies in mice. Together, these findings indicate that gentamicin C2b has reduced ototoxicity compared to clinically used preparations, supporting the need for further investigations in clinical settings.

Keywords

Aminoglycoside antibiotic; Gentamicin; Gentamicin C2b; Human induced pluripotent stem cells; Mouse auditory brainstem evoked response; Otic progenitor cells; Ototoxicity.

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