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Pharmacological regeneration of sensory hair cells restores afferent innervation and vestibular function
Hanae Lahlou, … , Wu Zhou, Albert S.B. Edge
Hanae Lahlou, … , Wu Zhou, Albert S.B. Edge
Published September 24, 2024
Citation Information: J Clin Invest. 2024;134(22):e181201. https://doi.org/10.1172/JCI181201.
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Research Article Otology Article has an altmetric score of 1

Pharmacological regeneration of sensory hair cells restores afferent innervation and vestibular function

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Abstract

The sensory cells that transduce the signals for hearing and balance are highly specialized mechanoreceptors called hair cells that together with supporting cells comprise the sensory epithelia of the inner ear. Loss of hair cells from toxin exposure and age can cause balance disorders and is essentially irreversible due to the inability of mammalian vestibular organs to regenerate physiologically active hair cells. Here, we show substantial regeneration of hair cells in a mouse model of vestibular damage by treatment with a combination of glycogen synthase kinase 3β and histone deacetylase inhibitors. The drugs stimulated supporting cell proliferation and differentiation into hair cells. The new hair cells were reinnervated by vestibular afferent neurons, rescuing otolith function by restoring head translation–evoked otolith afferent responses and vestibuloocular reflexes. Drugs that regenerate hair cells thus represent a potential therapeutic approach to the treatment of balance disorders.

Authors

Hanae Lahlou, Hong Zhu, Wu Zhou, Albert S.B. Edge

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Figure 3

SCs are the primary source of newly regenerated HCs.

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SCs are the primary source of newly regenerated HCs.
(A) Experimental st...
(A) Experimental strategy for fate mapping of SCs and HCs. Utricles from DT-ablated Pou4f3DTR/+-Plp1Cre-mTmG mice were harvested and cultured in CHV supplemented medium for 10 days. (B) Utricles immunolabeled for MYO7A (magenta) and SOX2 (blue). (C) High-magnification image indicating Plp mG+ and mG– expressing SCs (red and gray arrows), type I HCs (cyan arrow), and type II HCs (white arrow). (D) 3D reconstruction of optical sections showing the mapping of type I and type II HCs. (E) HC layer. (F) SC layer. (G) HC and SC mG+ and mG– counts from CHV-treated and -untreated utricles. (H) High-magnification images show a type I HC (I) and a type II HC (II) arising from Plp mG+ SCs (mG+). (I) High-magnification images of Plp mG+ and Plp mG– SCs (mG+ and mG–). All data represent the mean ± SEM. ***P < 0.001, ****P < 0.0001, by 2-tailed Student’s t test and 2-way ANOVA (G). Scale bar: 50 μm (B, images showing the whole utricle); 100 μm (C, H, and I). A, anterior; L, lateral; M, medial; P, posterior.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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