In vivo vocal fold cover layer replacement

AbstractVocal fold (VF) fibrosis is a major cause of intractable voice-related disability and reduced quality of life. Excision of fibrotic regions is suboptimal and associated with scar recurrence and/or further iatrogenic damage. Non-surgical interventions are limited, putatively related to limited insight regarding biochemical events underlying fibrosis, and downstream, the lack of therapeutic targets. YAP/TAZ integrates diverse cell signaling events and interacts with signaling pathways related to fibrosis, including the TGF-β/SMAD pathway. We investigated the expression of YAP/TAZ following vocal fold injury in vivo as well as the effects of TGF-β1 on YAP/TAZ activity in human vocal fold fibroblasts, fibroblast-myofibroblast transition, and TGF-β/SMAD signaling. Iatrogenic injury increased nuclear localization of YAP and TAZ in fibrotic rat vocal folds. In vitro, TGF-β1 activated YAP and TAZ in human VF fibroblasts, and inhibition of YAP/TAZ reversed TGF-β1-stimulated fibroplastic gene upregulation. Additionally, TGF-β1 induced localization of YAP and TAZ in close proximity to SMAD2/3, and nuclear accumulation of SMAD2/3 was inhibited by a YAP/TAZ inhibitor. Collectively, YAP and TAZ were synergistically activated with the TGF-β/SMAD pathway, and likely essential for the fibroplastic phenotypic shift in VF fibroblasts. Based on these data, YAP/TAZ may evolve as an attractive therapeutic target for VF fibrosis.

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Quantitative Evaluation of the In Vivo Vocal Fold Medial Surface Shape

Journal of Voice ◽

10.1016/j.jvoice.2016.12.004 ◽

2017 ◽

Vol 31 (4) ◽

pp. 513.e15-513.e23 ◽

Cited By ~ 8

Author(s):

Andrew M. Vahabzadeh-Hagh ◽

Zhaoyan Zhang ◽

Dinesh K. Chhetri

Keyword(s):

Quantitative Evaluation ◽

Vocal Fold ◽

Surface Shape ◽

Medial Surface

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In vivo investigation of acidified pepsin exposure to porcine vocal fold epithelia

The Laryngoscope ◽

10.1002/lary.25478 ◽

2015 ◽

Vol 126 (1) ◽

pp. E12-E17 ◽

Cited By ~ 7

Author(s):

Abigail Durkes ◽

M. Preeti Sivasankar

Keyword(s):

Vocal Fold

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Developmental derivation of vocal fold mucosa from human induced pluripotent stem cells

10.21203/rs.2.12611/v1 ◽

2019 ◽

Author(s):

Vlasta Lungova ◽

Susan Thibeault

Keyword(s):

Epithelial Cells ◽

Pluripotent Stem Cells ◽

Vocal Fold ◽

Fluorescent Protein ◽

Three Dimensional ◽

Stratified Squamous Epithelium ◽

Three Dimensional Models ◽

Induced Pluripotent ◽

Green Fluorescent

Abstract Development of treatments for vocal dysphonia has been inhibited by lack of human vocal fold (VF) mucosa models because of difficulty in procuring VF epithelial cells, epithelial cells’ limited proliferative capacity and absence of cell lines. We report development of engineered VF mucosae from hiPSC, transfected via TALEN constructs for green fluorescent protein, that mimic development of VF epithelial cells in utero. Modulation of FGF signaling achieves stratified squamous epithelium from definitive and anterior foregut derived cultures. Robust culturing of these cells on collagen-fibroblast constructs produces three-dimensional models comparable to in vivo VF mucosa.

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Toward Development of a Vocal Fold Contact Pressure Probe: Sensor Characterization and Validation Using Synthetic Vocal Fold Models

Applied Sciences ◽

10.3390/app9153002 ◽

2019 ◽

Vol 9 (15) ◽

pp. 3002 ◽

Cited By ~ 6

Author(s):

Mohsen Motie-Shirazi ◽

Matías Zañartu ◽

Sean D. Peterson ◽

Daryush D. Mehta ◽

James B. Kobler ◽

...

Keyword(s):

Contact Pressure ◽

Vocal Fold ◽

Ground Truth ◽

Pressure Probe ◽

Primary Role ◽

Novel Approach ◽

Sensor Position ◽

Probe Sensor ◽

Contact Pressures

Excessive vocal fold collision pressures during phonation are considered to play a primary role in the formation of benign vocal fold lesions, such as nodules. The ability to accurately and reliably acquire intraglottal pressure has the potential to provide unique insights into the pathophysiology of phonotrauma. Difficulties arise, however, in directly measuring vocal fold contact pressures due to physical intrusion from the sensor that may disrupt the contact mechanics, as well as difficulty in determining probe/sensor position relative to the contact location. These issues are quantified and addressed through the implementation of a novel approach for identifying the timing and location of vocal fold contact, and measuring intraglottal and vocal fold contact pressures via a pressure probe embedded in the wall of a hemi-laryngeal flow facility. The accuracy and sensitivity of the pressure measurements are validated against ground truth values. Application to in vivo approaches are assessed by acquiring intraglottal and VF contact pressures using a synthetic, self-oscillating vocal fold model in a hemi-laryngeal configuration, where the sensitivity of the measured intraglottal and vocal fold contact pressure relative to the sensor position is explored.

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