Mesenchymal Stem Cell Therapy for the Treatment of Vocal Fold Scarring: A Systematic Review of Preclinical Studies.

Christian Grønhøj Larsen,Christian Von Buchwald,David H Jensen,Graca D Almeida-Porada,Anne Fischer-Nielsen,Kristian Bork,Lars Sebbesen,Vibe Lindeblad Wingstrand,Jesper Balle

doi:10.1371/journal.pone.0162349

Christian Grønhøj Larsen, Christian Von Buchwald + Show 7 more

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https://doi.org/10.1371/journal.pone.0162349

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Abstract

ObjectivesTherapy with mesenchymal stem cells exhibits potential for the development of novel interventions for many diseases and injuries. The use of mesenchymal stem cells in regenerative therapy for vocal fold scarring exhibited promising results to reduce stiffness and enhance the biomechanical properties of injured vocal folds. This study evaluated the biomechanical effects of mesenchymal stem cell therapy for the treatment of vocal fold scarring.Data SourcesPubMed, Embase, the Cochrane Library and Google Scholar were searched.MethodsControlled studies that assessed the biomechanical effects of mesenchymal stem cell therapy for the treatment of vocal fold scarring were included. Primary outcomes were viscoelastic properties and mucosal wave amplitude.ResultsSeven preclinical animal studies (n = 152 single vocal folds) were eligible for inclusion. Evaluation of viscoelastic parameters revealed a decreased dynamic viscosity (η’) and elastic modulus (G’), i.e., decreased resistance and stiffness, in scarred vocal folds treated with mesenchymal stem cells compared to non-treated scarred vocal folds. Mucosal wave amplitude was increased in scarred vocal folds treated with mesenchymal stem cells vs. non-treated scarred vocal folds.ConclusionThe results from these studies suggest an increased regenerative effect of therapy with mesenchymal stem cells for scarred vocal folds and are encouraging for further clinical studies.

Highlights

Parts of normal vocal fold (VF) tissue are often replaced with scar tissue during the healing process after trauma, inflammatory disorders, iatrogenic lesions after surgery, and as a wellknown side-effect of the treatment of head and neck cancers with radiotherapy.[1]The tissue in the wound healing process after any type of insult may be replaced by fibrous scar tissue, which primarily consists of an excessive, disorganized extracellular matrix
Controlled studies that assessed the biomechanical effects of mesenchymal stem cell therapy for the treatment of vocal fold scarring were included
Evaluation of viscoelastic parameters revealed a decreased dynamic viscosity (η’) and elastic modulus (G’), i.e., decreased resistance and stiffness, in scarred vocal folds treated with mesenchymal stem cells compared to non-treated scarred vocal folds

Summary

Introduction

The tissue in the wound healing process after any type of insult may be replaced by fibrous scar tissue, which primarily consists of an excessive, disorganized extracellular matrix. The scar tissue matrix is generally stiffer than the extracellular matrix it replaces This matrix is of particular concern in areas surrounding and including the vocal folds because the normal functions of these tissues depend on their elastic and vibratory properties. Changes in the extracellular matrix, such as the change from highly organized elastin to disorganized Type I collagen, primarily explain the change in phonation.[5] The altered composition of ECM proteins is observed microscopically and correlates with macroscopically altered biomechanical properties, which lead to changes in the mucosal waves during phonation.[6,7,8] Notably, these altered biomechanical properties predict the quality of phonation.[6]

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