Regeneration of the Vocal Fold Using Autologous Mesenchymal Stem Cells

Kanemaru, Shin‐ichi; Kojima, Hisayoshi; Hirano, Shigeru; Nakamura, Tatsuo; Magrufov, Akhmar; Ito, Juichi; Omori, Koichi; Hiratsuka, Yasuyuki; Shimizu, Yasuhiko

doi:10.1177/000348940311201101

Cited by 140 publications

(37 citation statements)

References 29 publications

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“…Histologic and rheologic assays were performed three months post-injury and revealed reduced collagen abundance, reduced lamina propria thickness, and improved dynamic viscosity compared to saline-treated controls. These promising findings align with earlier work published by this research group and others [25, 26]. …”

Section: Treatmentsupporting

confidence: 93%

Characterization of vocal fold scar formation, prophylaxis, and treatment using animal models

Bless

Welham

2010

Current Opinion in Otolaryngology &Amp; Head &Amp; Neck Surgery

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Purpose of review This article reviews recent literature on animal models used to study the pathogenesis, detection, prevention and treatment of vocal fold scarring. Animal work is critical to studying vocal fold scarring because it is the only way to conduct systematic research on the biomechanical properties of the layered structure of the vocal fold lamina propria, and therefore develop reliable prevention and treatment strategies for this complex clinical problem. Recent findings During the period of review, critical anatomic, physiologic and wound healing characteristics, which may serve as the bases for selection of a certain species to help answer a specific question, have been described in mouse, rat, rabbit, ferret and canine models. A number of different strategies for prophylaxis and chronic scar treatment in animals show promise for clinical application. The pathways of scar formation and methods for quantifying treatment-induced change have become better defined. Summary Recent animal vocal fold scarring studies have enriched and confirmed earlier work indicating that restoring pliability to the scarred vocal fold mucosa is challenging but achievable. Differences between animal models and differences in outcome measurements across studies necessitate considering each study individually to obtain guidance for future research. With increased standardization of measurement techniques it may be possible to make more inter-study comparisons.

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Section: Treatmentsupporting

confidence: 93%

Characterization of vocal fold scar formation, prophylaxis, and treatment using animal models

Bless

Welham

2010

Current Opinion in Otolaryngology &Amp; Head &Amp; Neck Surgery

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“…[54,56,92] Kanemaru et al was the first to report the therapeutic benefit of injecting autologous MSCs encapsulated in 1% hydrochloric acid atelocollagen to facilitate the regeneration of injured canine vocal folds. [93] The observed in vivo cell proliferation within the atelocollagen scaffold indicated that atelocollagen is suitable for vocal fold tissue engineering. Kishimoto et al continued to investigate the restorative effects of a scaffold on vocal fold scarring and sulcus vocalis by implanting atelocollagen sheet into patients with post-cordectomy scar or sulcus vocalis.…”

Section: Biomaterials In Development/researchmentioning

confidence: 99%

Tissue engineering-based therapeutic strategies for vocal fold repair and regeneration

Stiadle

Lau

et al. 2016

Biomaterials

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Vocal folds are soft laryngeal connective tissues with distinct layered structures and complex multicomponent matrix compositions that endow phonatory and respiratory functions. This delicate tissue is easily damaged by various environmental factors and pathological conditions, altering vocal biomechanics and causing debilitating vocal disorders that detrimentally affect the daily lives of suffering individuals. Modern techniques and advanced knowledge of regenerative medicine have led to a deeper understanding of the microstructure, microphysiology, and micropathophysiology of vocal fold tissues. State-of-the-art materials ranging from extracecullar-matrix (ECM)-derived biomaterials to synthetic polymer scaffolds have been proposed for the prevention and treatment of voice disorders including vocal fold scarring and fibrosis. This review intends to provide a thorough overview of current achievements in the field of vocal fold tissue engineering, including the fabrication of injectable biomaterials to mimic in vitro cell microenvironments, novel designs of bioreactors that capture in vivo tissue biomechanics, and establishment of various animal models to characterize the in vivo biocompatibility of these materials. The combination of polymeric scaffolds, cell transplantation, biomechanical stimulation, and delivery of antifibrotic growth factors will lead to successful restoration of functional vocal folds and improved vocal recovery in animal models, facilitating the application of these materials and related methodologies in clinical practice.

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“…45 Mesenchymal stem cells have already been shown to have useful properties in the regeneration of damaged vocal folds. 46 Although it is unknown if the preepiglottic space fat donated to CTAP contains a population of mesenchymal stem cells, certainly the notion of presenting a damaged vocal fold with a fresh population of stem cells is attractive.…”

Section: Discussionmentioning

confidence: 99%

Local vascularized flaps for augmentation of reinke's space

Dailey¹,

Gunderson²,

Chan³

et al. 2011

The Laryngoscope

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Objectives/Hypothesis The purpose of this study is to describe and test a novel surgical strategy for augmentation of Reinke’s space using vascularized flaps: a thyroid ala perichondrium flap (TAP) and a composite thyroid ala perichondrium flap (CTAP) from the anterior larynx. We hypothesized that these specially designed vascularized flaps would remain viable once inset into the lamina propria, and that they would not disrupt rheologic, biomechanical, and histologic properties of the native vocal fold. Study Design Experimental. In vivo canine model. Methods The length and volume of test flaps harvested in six adult human cadaveric larynges were analyzed to determine suitability for use in augmentation in the lamina propria. Also, 12 beagles randomly underwent unilateral placement of either TAP or CTAP, which were designed in accordance with the human adult cadaveric experiments. Flap perfusion was measured before and after harvest with laser Doppler. After 1 month, the beagles were humanely sacrificed and their larynges subjected to aerodynamic and acoustic evaluation using an excised larynx apparatus. The vocal fold lamina propria of four larynges—two TAP and two CTAP—underwent rheologic evaluation using a simple-shear rheometer. The remaining eight larynges underwent quantitative histologic and immunohistochemical evaluation. The survival and complication (swallowing, airway, local wound) rates of all dogs were noted. Results Initial studies with adult human cadaveric larynges established that TAP and CTAP possessed length and volume greater than native lamina propria. In the canine experiments, the perfusion change in the flaps was similar between flap groups. The damping ratio (ζ), dynamic viscosity (η′), elastic shear modulus (G′), and viscous shear modulus (G″) of treated and untreated native vocal folds were not statistically different. The glottic function measures of vocal efficiency, laryngeal resistance, jitter, shimmer, and harmonics-to-noise ratio (HNR) of treated and normal larynges were not statistically different. Similarly, the values for collagen, elastin, and glycosaminoglycans (GAGs) in treated and untreated vocal folds were not statistically different. Also, neither neochrondrogenesis nor neoosteogenesis was detected in any treated vocal fold. The values for vascular and cellular proliferation in treated and untreated vocal folds were not statistically different. All test dogs survived and had no complications related to swallowing, airway distress, or the local wound. Conclusions The test flaps described and tested in this study appear to have conceptually attractive features for augmentation of Reinke’s space. When placed in an in vivo setting TAP and CTAP did not reveal unfavorable vascular, rheologic, aerodynamic, acoustic, or histologic characteristics. There was no unanticipated morbidity or mortality to the test animals. Long-term viability of these flaps is unknown. TAP and CTAP may open novel pathways for correction of glottic defects and may offer crossover opportunities...

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Regeneration of the Vocal Fold Using Autologous Mesenchymal Stem Cells

Cited by 140 publications

References 29 publications

Characterization of vocal fold scar formation, prophylaxis, and treatment using animal models

Characterization of vocal fold scar formation, prophylaxis, and treatment using animal models

Tissue engineering-based therapeutic strategies for vocal fold repair and regeneration

Local vascularized flaps for augmentation of reinke's space

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