Author:
van der Valk Wouter H.,Steinhart Matthew R.,Zhang Jingyuan,Koehler Karl R.
Abstract
AbstractWhile inner ear disorders are common, our ability to intervene and recover their sensory function is limited. In vitro models of the inner ear, like the organoid system, could aid in identifying new regenerative drugs and gene therapies. Here, we provide a perspective on the status of in vitro inner ear models and guidance on how to improve their applicability in translational research. We highlight the generation of inner ear cell types from pluripotent stem cells as a particularly promising focus of research. Several exciting recent studies have shown how the developmental signaling cues of embryonic and fetal development can be mimicked to differentiate stem cells into “inner ear organoids” containing otic progenitor cells, hair cells, and neurons. However, current differentiation protocols and our knowledge of embryonic and fetal inner ear development in general, have a bias toward the sensory epithelia of the inner ear. We propose that a more holistic view is needed to better model the inner ear in vitro. Moving forward, attention should be made to the broader diversity of neuroglial and mesenchymal cell types of the inner ear, and how they interact in space or time during development. With improved control of epithelial, neuroglial, and mesenchymal cell fate specification, inner ear organoids would have the ability to truly recapitulate neurosensory function and dysfunction. We conclude by discussing how single-cell atlases of the developing inner ear and technical innovations will be critical tools to advance inner ear organoid platforms for future pre-clinical applications.
Funder
U.S. Department of Health & Human Services | NIH | National Institute on Deafness and Other Communication Disorders
U.S. Department of Defense
Publisher
Springer Science and Business Media LLC
Subject
Cell Biology,Molecular Biology
Reference130 articles.
1. WHO. Fact sheet: deafness and hearing loss. https://www.who.int/news-room/fact-sheets/detail/deafness-and-hearing-loss. 2020; Accessed 1 Jul 2020.
2. Hülse R, Biesdorf A, Hörmann K, Stuck B, Erhart M, Hülse M, et al. Peripheral vestibular disorders: an epidemiologic survey in 70 million individuals. Otol Neurotol. 2019;40:88–95.
3. Géléoc GSG, Holt JR. Sound strategies for hearing restoration. Science. 2014;344:1241062.
4. Delmaghani S, El-Amraoui A. Inner ear gene therapies take off: current promises and future challenges. J Clin Med. 2020;9:2309.
5. Ganesan P, Schmiedge J, Manchaiah V, Swapna S, Dhandayutham S, Kothandaraman PP. Ototoxicity: a challenge in diagnosis and treatment. J Audiol Otol. 2018;22:59–68.
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