scholarly journals Liquid-type non-thermal atmospheric plasma ameliorates vocal fold scarring by modulating vocal fold fibroblast

2019 ◽  
Vol 244 (10) ◽  
pp. 824-833 ◽  
Author(s):  
Ho-Ryun Won ◽  
Eun Hye Song ◽  
Jong Eun Won ◽  
Hye Young Lee ◽  
Sung Un Kang ◽  
...  
Keyword(s):  
Vocal Fold ◽  
Therapeutic Agent ◽  
Transforming Growth Factor ◽  
Therapeutic Option ◽  
Vocal Folds ◽  
Atmospheric Plasma ◽  
Matrix Metalloproteinase 2 ◽  
Functional Improvement ◽  
Voice Disorder ◽  
Liquid Type

Injection laryngoplasty is a widely used therapeutic option for drug delivery into vocal folds (VFs). Efficient injectable materials are urgently needed for treating intractable VF disease. Liquid-type non-thermal atmospheric plasma (LTP) has been found to be useful for various biological applications, including in regenerative medicine. We evaluated the effects of LTP on VF regeneration. Migration and matrix metalloproteinase-2 expression of lipopolysaccharide (LPS)-treated human vocal fold-derived mesenchymal stem cells (VF-MSCs) were enhanced by LTP treatment. LTP treatment not only ameliorated nuclear factor-κB and interleukin-6 activation, induced by LPS treatment, but also the increased manifestation of α-smooth muscle actin and fibronectin, induced by transforming growth factor-ß. In a rabbit VF scarring animal model, histological analyses showed increased hyaluronic acid deposition and decreased collagen accumulation after LTP injection. Videokymographic analysis showed more improved vibrations in LTP-treated VF mucosa compared to those in non-treated group. In conclusion, LTP treatment enhanced the recruitment and activation of VF-MSCs. Regulated extracellular matrix (ECM) synthesis and eventual functional improvement of scarred VFs were observed upon LTP treatment. The results of this study suggest that LTP injection can enhance wound healing and improve functional remodeling following VF injury. Impact statement Voice disorder has a significant impact on life quality, and one of the major causes of this voice disorder is vocal fold scarring. Therefore, various approaches have been tried to treat for voice disorder. However, no method has satisfied all requirements until now. Plasma medicine, which involves the medical application of plasma, is a rapidly developing field. We have confirmed that liquid-type plasma improved vocal fold scarring by mobilizing and activating vocal fold fibroblast. In conclusion, liquid-type plasma is a potential therapeutic agent for promoting vocal fold scarring through simple injection and it may be an alternative therapeutic agent for the current situation to treat voice disorder.

Videostrobolaryngoscopy of Mucus Layer during Vocal Fold Vibration in Patients with Laryngeal Tension-Fatigue Syndrome

2002 ◽  
Vol 111 (6) ◽  
pp. 537-541 ◽  
Author(s):  
Tzu-Yu Hsiao ◽  
Chia-Ming Liu ◽  
Kai-Nan Lin
Keyword(s):  
Mechanical Properties ◽  
Vocal Fold ◽  
Rough Surfaces ◽  
Voice Disorders ◽  
Vocal Folds ◽  
Voice Disorder ◽  
Mucus Layer ◽  
Vocal Fold Vibration ◽  
Fatigue Syndrome ◽  
Functional Dysphonia

The mucus layer on the vocal folds was examined by videostrobolaryngoscopy in patients with laryngeal tension-fatigue syndrome, a chronic functional dysphonia due to vocal abuse and misuse. Besides the findings in previous reports (such as abnormal glottal closure, phase or amplitude asymmetry, and the irregular mucosal wave), the vocal folds during vibration had an uneven mucus surface. The occurrence of an uneven mucus layer on vocal folds was significantly greater in subjects with this voice disorder (83% or 250 of 301 patients in this series) than in those without voice disorders (18.5% or 5 of 27). The increase of mucus viscosity, mucus aggregation, and the formation of rough surfaces on the vocal folds alter the mechanical properties that contribute to vibration of the cover of the vocal folds, and thereby worsen the symptoms of dysphonia in patients with laryngeal tension-fatigue syndrome.

Effect of Exogenous Hepatocyte Growth Factor on Vocal Fold Fibroblasts

2009 ◽  
Vol 118 (8) ◽  
pp. 606-611 ◽  
Author(s):  
Yo Kishimoto ◽  
Shigeru Hirano ◽  
Atsushi Suehiro ◽  
Ichiro Tateya ◽  
Shin-Ichi Kanemaru ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Vocal Fold ◽  
Transforming Growth Factor ◽  
Therapeutic Potential ◽  
Vocal Folds ◽  
Messenger Rnas ◽  
Extracellular Matrix Components ◽  
Hepatocyte Growth ◽  
Tgf Β1

Objectives We have previously demonstrated the therapeutic potential of hepatocyte growth factor (HGF) in the treatment of vocal fold scarring, although how exogenous HGF affects gene expression of endogenous HGF or extracellular matrix components in the vocal fold fibroblasts remains unclear. In this in vitro study, we aimed to clarify this aspect in order to better understand the effects of HGF on the vocal folds. Methods Fibroblasts were obtained from the lamina propria of the vocal folds of 5 Sprague-Dawley rats and were cultured with HGF at concentrations of 100, 10, 1, and 0 ng/mL. The cells were collected on days 1, 3, and 7, and the expression of endogenous HGF, its receptor c-Met, transforming growth factor-β1 (TGF-β1), procollagen types I and III, and hyaluronic acid synthase (HAS)-l and HAS-2 messenger RNAs (mRNAs) was examined by real-time reverse transcription-polymerase chain reaction. Results The expression of endogenous HGF and HAS-1 mRNAs increased significantly when exogenous HGF was administered at a concentration of 1 ng/mL. On day 1, the expression of TGF-β1 and HAS-2 mRNAs increased significantly in response to 1 ng/mL HGF. Conclusions Exogenous HGF triggered the up-regulation of endogenous HGF, TGF-β1, HAS-1, and HAS-2 mRNAs in vocal fold fibroblasts.

scholarly journals In vitro mechanical vibration down-regulates pro-inflammatory and pro-fibrotic signaling in human vocal fold fibroblasts

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0241901
Author(s):  
David Hortobagyi ◽  
Tanja Grossmann ◽  
Magdalena Tschernitz ◽  
Magdalena Grill ◽  
Andrijana Kirsch ◽  
...  
Keyword(s):  
Vocal Fold ◽  
Transforming Growth Factor ◽  
Vibrational Excitation ◽  
Smooth Muscle Actin ◽  
Mechanical Vibration ◽  
Vocal Folds ◽  
Alpha Smooth Muscle Actin ◽  
Protein Levels ◽  
Inflammatory Conditions

Introduction Voice rest following phonotrauma or phonosurgery has a considerable clinical impact, but clinical recommendations are inconsistent due to inconclusive data. As biopsies of the vocal folds (VF) for molecular biology studies in humans are unethical, we established a new in vitro model to explore the effects of vibration on human vocal fold fibroblasts (hVFF) in an inflammatory and normal state, which is based on previously published models. Methods By using a phonomimetic bioreactor we were able to apply predefined vibrational stress patterns on hVFF cultured under inflammatory or normal conditions. Inflammatory and pro-fibrotic stimuli were induced by interleukin (IL)1β and transforming growth factor (TGF)β1, respectively. Mechanical stimulation was applied four hours daily, over a period of 72 hours. Outcome measurements comprised assessment of extracellular matrix (ECM)-related components, angiogenic factors, and inflammatory and fibrogenic markers on gene expression and protein levels. Results Under inflammatory conditions, the inflammatory cytokine IL11, as well as the myofibroblast marker alpha smooth muscle actin (α-SMA) were significantly reduced when additional vibration was applied. The desirable anti-fibrotic ECM component hyaluronic acid was increased following cytokine treatment, but was not diminished following vibration. Conclusion Our experiments revealed the effect of vibrational stress on hVFF in an inflammatory state. Elevated levels of certain pro-inflammatory/pro-fibrotic factors could be mitigated by additional vibrational excitation in an in vitro setting. These findings corroborate clinical studies which recommend early voice activation following an acute event.

scholarly journals The Effect of Fibroblast Growth Factors in Grafted Fascia into the Vocal Fold of Rabbits

2018 ◽  
Vol 23 (01) ◽  
pp. 060-064
Author(s):  
Eduardo Carvalho ◽  
Almiro Machado-Júnior ◽  
Henrique Pauna ◽  
Ester Nicola ◽  
Albina Altemani ◽  
...  
Keyword(s):  
Growth Factors ◽  
Lamina Propria ◽  
Vocal Fold ◽  
Therapeutic Option ◽  
Fibroblast Growth Factors ◽  
Vocal Folds ◽  
Fibroblast Growth ◽  
Initial Experiment ◽  
Inflammatory Reactions ◽  
Tissue Integration

Introduction The human larynx is a very important organ for communication. Many conditions lead to scarring of the vocal folds, decreasing voice quality. Objective We aimed to determine whether fibroblast growth factors (FGFs) may influence tissue integration of grafted fascia into the vocal folds of an animal model. Methods This is an experimental animal study with 12 adult rabbits that were submitted to a grafting fragment obtained from superficial cervical fascia into the vocal fold lamina propria, bilaterally. The right vocal fold was injected with FGFs. The animals were sacrificed after 1 month or 12 months, depending on the group they were assigned to, and a histological analysis of their vocal folds was performed. We analyzed the histological changes (such as the presence of fibrosis and neovascularization) induced by the acute or chronic inflammatory reactions. Results The FGFs induced acute inflammatory changes in all animals after 1 month of the initial experiment. The presence of FGFs triggered more fibrosis than the expected due to the surgical procedure itself when compared with the control side of all animals after 12 months of the initial experiment. Conclusions Fibroblast growth factors alone do not represent a good therapeutic option in phonosurgery, since we observed higher levels of fibrosis in the vocal fold lamina propria. Further studies combining more substances may be necessary to elucidate the best option to be used in this kind of surgery.

Effect of Growth Factors on Hyaluronan Production by Canine Vocal Fold Fibroblasts

2003 ◽  
Vol 112 (7) ◽  
pp. 617-624 ◽  
Author(s):  
Shigeru Hirano ◽  
Dennis Heisey ◽  
Diane M. Bless ◽  
Charles N. Ford
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Lamina Propria ◽  
Vocal Fold ◽  
Transforming Growth Factor ◽  
Vocal Folds ◽  
Transforming Growth Factor Β1 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Positive Effects

Hyaluronan (HYA) is considered to be a crucial factor in scarless wound healing and in maintaining tissue viscosity of the vocal fold lamina propria. In this study focusing on the effects of growth factors, we examined how HYA is produced and controlled in canine cultured vocal fold fibroblasts. Fibroblasts were taken from the lamina propria of the vocal folds of 8 dogs and cultured with and without growth factors. The production of HYA in the supernatant culture was quantitatively examined by enzyme-linked immunosorbent assay. Hepatocyte growth factor, epidermal growth factor, basic fibroblast growth factor, and transforming growth factor β1 all stimulated HYA synthesis from vocal fold fibroblasts. These effects differed with the concentration of growth factors and the incubation period. We also examined how frequently the growth factors had to be administered in order to maintain appropriate levels of HYA. A single administration was sufficient to maintain appropriate HYA levels for at least 7 days. The present studies have demonstrated positive effects of growth factors in stimulating HYA production. Further in vivo study is needed to clarify the usefulness of these growth factors in the management of vocal fold scarring.

Assessment of Tongue Position and Laryngeal Height in Two Professional Voice Populations

2020 ◽  
Vol 63 (1) ◽  
pp. 109-124
Author(s):  
Carly Jo Hosbach-Cannon ◽  
Soren Y. Lowell ◽  
Raymond H. Colton ◽  
Richard T. Kelley ◽  
Xue Bao
Keyword(s):  
Vocal Fold ◽  
Vocal Tract ◽  
Current Knowledge ◽  
Acoustic Resonance ◽  
Contact Dynamics ◽  
Voice Disorder ◽  
Music Program ◽  
Tongue Position ◽  
Singer Groups ◽  
Professional Voice

Purpose To advance our current knowledge of singer physiology by using ultrasonography in combination with acoustic measures to compare physiological differences between musical theater (MT) and opera (OP) singers under controlled phonation conditions. Primary objectives addressed in this study were (a) to determine if differences in hyolaryngeal and vocal fold contact dynamics occur between two professional voice populations (MT and OP) during singing tasks and (b) to determine if differences occur between MT and OP singers in oral configuration and associated acoustic resonance during singing tasks. Method Twenty-one singers (10 MT and 11 OP) were included. All participants were currently enrolled in a music program. Experimental procedures consisted of sustained phonation on the vowels /i/ and /ɑ/ during both a low-pitch task and a high-pitch task. Measures of hyolaryngeal elevation, tongue height, and tongue advancement were assessed using ultrasonography. Vocal fold contact dynamics were measured using electroglottography. Simultaneous acoustic recordings were obtained during all ultrasonography procedures for analysis of the first two formant frequencies. Results Significant oral configuration differences, reflected by measures of tongue height and tongue advancement, were seen between groups. Measures of acoustic resonance also showed significant differences between groups during specific tasks. Both singer groups significantly raised their hyoid position when singing high-pitched vowels, but hyoid elevation was not statistically different between groups. Likewise, vocal fold contact dynamics did not significantly differentiate the two singer groups. Conclusions These findings suggest that, under controlled phonation conditions, MT singers alter their oral configuration and achieve differing resultant formants as compared with OP singers. Because singers are at a high risk of developing a voice disorder, understanding how these two groups of singers adjust their vocal tract configuration during their specific singing genre may help to identify risky vocal behavior and provide a basis for prevention of voice disorders.

scholarly journals Concurrent YAP/TAZ and SMAD signaling mediate vocal fold fibrosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ryosuke Nakamura ◽  
Nao Hiwatashi ◽  
Renjie Bing ◽  
Carina P. Doyle ◽  
Ryan C. Branski
Keyword(s):  
Vocal Fold ◽  
Vocal Folds ◽  
Nuclear Accumulation ◽  
Smad Pathway ◽  
Surgical Interventions ◽  
Smad Signaling ◽  
Iatrogenic Damage ◽  
Tgf Β1

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.

scholarly journals Ileocolonic Healing After Extended Small Bowel Resection in Mice: NOD2 Deficiency Impairs Anastomotic Healing and Postoperative Outcome

2021 ◽  
Author(s):  
Maria Witte ◽  
Johannes Reiner ◽  
Karen Bannert ◽  
Robert Jaster ◽  
Christian Maschmeier ◽  
...  
Keyword(s):  
Gene Expression ◽  
Crohn Disease ◽  
Transforming Growth Factor ◽  
Bowel Resection ◽  
Anastomotic Healing ◽  
Matrix Metalloproteinase 2 ◽  
Ileocecal Resection ◽  
Bursting Pressure ◽  
Septic Complications ◽  
Gelatinase Activity

Abstract Background Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) mutations are a genetic risk factor for Crohn disease. Ileocecal resection is the most often performed surgery in Crohn disease. We investigated the effect of Nod2 knockout (KO) status on anastomotic healing after extended ileocecal resection (ICR) in mice. Methods Male C57BL6/J wild-type and Nod2 KO mice underwent an 11 cm resection of the terminal ileum including the cecum. An end-to-end jejuno-colostomy was performed. Animals were killed after 5 days investigating bursting pressure, hydroxyproline content, and expression of matrix metabolism genes, key cytokines, and histology of the anastomosis. Results Mortality was higher in the Nod2 KO group but not because of local or septic complications. Bursting pressure was significantly reduced in the Nod2 KO mice (32.5 vs 78.0 mmHg, P < 0.0024), whereas hydroxyprolin content was equal. The amount of granulation tissue at the anastomosis was similar but more unstructured in the Nod2 KO mice. Gene expression measured by real-time polymerase chain reaction showed significantly increased expression for Collagen 1alpha and for collagen degradation as measured by matrix metalloproteinase-2, -9, and -13 in the Nod2 KO mice. Gelatinase activity from anastomotic tissue was enhanced by Nod2 status. Gene expression of arginase I, tumor necrosis factor-α, and transforming growth factor-ß but not inducible nitric oxide synthase were also increased at the anastomosis in the Nod2 KO mice compared with the control mice. Conclusions We found that Nod2 deficiency results in significantly reduced bursting pressure after ileocecal resection. This effect is mediated via an increased matrix turnover. Patients with genetic NOD2 variations may be prone to anastomotic failure after bowel resection.

scholarly journals Therapeutic Features and Updated Clinical Trials of Mesenchymal Stem Cell (MSC)-Derived Exosomes

2021 ◽  
Vol 10 (4) ◽  
pp. 711
Author(s):  
Byung-Chul Lee ◽  
Insung Kang ◽  
Kyung-Rok Yu
Keyword(s):  
Clinical Trials ◽  
Therapeutic Agent ◽  
Therapeutic Potential ◽  
Therapeutic Option ◽  
Treatment Options ◽  
Genetic Material ◽  
Experimental Models ◽  
Attractive Alternative ◽  
Cell Based Therapy ◽  
Cellular Rejection

Identification of the immunomodulatory and regenerative properties of mesenchymal stem cells (MSCs) have made them an attractive alternative therapeutic option for diseases with no effective treatment options. Numerous clinical trials have followed; however, issues such as infusional toxicity and cellular rejection have been reported. To address these problems associated with cell-based therapy, MSC exosome therapy was developed and has shown promising clinical outcomes. MSC exosomes are nanosized vesicles secreted from MSCs and represent a non-cellular therapeutic agent. MSC exosomes retain therapeutic features of the cells from which they originated including genetic material, lipids, and proteins. Similar to MSCs, exosomes can induce cell differentiation, immunoregulation, angiogenesis, and tumor suppression. MSC exosomes have therefore been employed in several experimental models and clinical studies. Here, we review the therapeutic potential of MSC-derived exosomes and summarize currently ongoing clinical trials according to disease type. In addition, we propose several functional enhancement strategies for the effective clinical application of MSC exosome therapy.

High-Speed Imaging to Study an Auto-Oscillating Vocal Fold Replica for Different Initial Conditions

2017 ◽  
Vol 09 (05) ◽  
pp. 1750064 ◽  
Author(s):  
A. Van Hirtum ◽  
X. Pelorson
Keyword(s):  
Vocal Fold ◽  
High Speed ◽  
Initial Conditions ◽  
Vocal Folds ◽  
High Speed Imaging ◽  
Human Voice ◽  
Manual Intervention ◽  
Geometrical Features ◽  
Upstream Pressure

Experiments on mechanical deformable vocal folds replicas are important in physical studies of human voice production to understand the underlying fluid–structure interaction. At current date, most experiments are performed for constant initial conditions with respect to structural as well as geometrical features. Varying those conditions requires manual intervention, which might affect reproducibility and hence the quality of experimental results. In this work, a setup is described which allows setting elastic and geometrical initial conditions in an automated way for a deformable vocal fold replica. High-speed imaging is integrated in the setup in order to decorrelate elastic and geometrical features. This way, reproducible, accurate and systematic measurements can be performed for prescribed initial conditions of glottal area, mean upstream pressure and vocal fold elasticity. Moreover, quantification of geometrical features during auto-oscillation is shown to contribute to the experimental characterization and understanding.

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