ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026
Cryopreserved Human Otic Neuronal Spheroids Self-assemble for Functional Connectivity Analysis and Long-term Ototoxicity Evaluation.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
4 citing papers in PubMed.
- Piezoelectric Nanofibrous Scaffolds for Promoting the Growth of Spiral Ganglion Neurons via Acoustic Stimulation.Smart medicine · 2026Article
- Cryopreserved Human Otic Neuronal Spheroids Self-assemble for Functional Connectivity Analysis and Long-term Ototoxicity Evaluation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Advances and prospects of 3D air-liquid interface cultured middle ear epithelial cells and inner ear organoids in otologic diseases.Frontiers in bioengineering and biotechnology · 2026Review
- Targeting ferroptosis in sensorineural hearing loss: mechanisms, therapeutics, and translational prospects.Frontiers in neurologyReview
Corrections and comments
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Authors and funding
16 authors.
Funding
Abstract
Spiral ganglion neurons (SGNs) in the inner ear are indispensable for auditory function, and their irreversible damage causes permanent sensorineural hearing loss. Although current human pluripotent stem cell (hPSC)-derived otic lineages offer a valuable resource for SGN regeneration, they face challenges in terms of reproducibility and functional maturation. Here, a robust protocol is established to generate human otic neuronal spheroids (hONS) from cryopreserved hPSC-derived pre-placodal ectoderm (PPE) cells. Post-thaw PPE cells retained high purity and differentiation efficiency comparable to fresh PPE cells. These self-assembled hONS differentiated into functionally mature SGN-like neurons, showing specific maker expression, electrophysiological activity, AMPA receptor-mediated glutamate response, and extensive neurite extension. In tripartite cocultures incorporating murine cochlear explants and human cortical organoids, hONS formed bidirectional functional synaptic connections, validated through live-cell imaging, optogenetic stimulation, and synaptic immunostaining. Notably, hONS exhibited heightened sensitivity to ototoxic insults. Short-term cisplatin exposure induced dose-dependent alterations in cellular and calcium dynamics, whereas prolonged exposure impaired glutamatergic neural functionality and triggered progressive neuronal death. Co-treatment with sodium thiosulfate attenuated cisplatin-induced damage. The hONS model also demonstrated concentration-dependent toxicity to neomycin. Collectively, this hONS model provides a reliable platform for investigating SGN regeneration and conducting preclinical evaluation of ototoxic drug.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.