Osborn, A, Caruana, D, Furness, DN and Evans, MG (2022) Electrical and immunohistochemical properties of cochlear fibrocytes in 3D cell culture and in the excised spiral ligament of mice. JARO: Journal of the Association for Research in Otolaryngology, 23 (2). pp. 183-193.

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Abstract

Fibrocyte degeneration in the cochlear lateral wall is one possible pathology of age-related metabolic hearing loss (presbycusis). Within the lateral wall fibrocytes play a role in potassium recycling and maintenance of the endocochlear potential. It has been proposed that cell replacement therapy could prevent fibrocyte degeneration in the CD/1 mouse model of hearing loss. For this to work, the replacement fibrocytes would need to take over the structural and physiological role of those lost. We have grown lateral wall fibrocytes from neonatal CD/1 mice in a 3D collagen gel culture with the aim of assessing their functional similarity to native lateral wall fibrocytes, the latter in a slice preparation and in excised spiral ligament pieces. We have compared cultured and native fibrocytes using both immuno-labelling of characteristic proteins and single cell electrophysiology. Cultured fibrocytes exhibited rounded cell bodies with extending processes. They labelled with marker antibodies targeting aquaporin 1 and calcium-binding protein S-100, precluding an unambiguous identification of fibrocyte type. In whole-cell voltage clamp, both native and cultured fibrocytes exhibited non-specific currents and voltage-dependent K+ currents. The non-specific currents from gel-cultured and excised spiral ligament fibrocytes were partially and reversibly blocked by external TEA (10 mM). The TEA-sensitive current had a mean reversal potential of +26 mV, suggesting a permeability sequence of Na+ > K+. These findings indicate that 3D cultured fibrocytes share a number of characteristics with native spiral ligament fibrocytes and thus might represent a suitable population for transplantation therapy aimed at treating age-related hearing loss.

Item Type: Article
Additional Information: The final version of this accepted manuscript and all relevant information related to it, including copyrights, can be found on the publisher website.
Uncontrolled Keywords: Cochlea; Fibrocyte; Collagen hydrogel; Immunolabelling; Whole-cell recording
Subjects: R Medicine > R Medicine (General)
R Medicine > RS Pharmacy and materia medica
Divisions: Faculty of Natural Sciences > School of Life Sciences
Depositing User: Symplectic
Date Deposited: 07 Jan 2022 09:40
Last Modified: 19 Apr 2022 09:12
URI: https://eprints.keele.ac.uk/id/eprint/10469

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