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Vocal fold myofibroblast profile of scarring.

ABSTRACT: Vocal fold fibroblasts (VFF) are responsible for extracellular matrix synthesis supporting lamina propria in normal and diseased conditions. When tissue is injured, VFF become activated and differentiate into myofibroblasts to facilitate wound healing response. We investigated if vocal fold myofibroblasts can be utilized as surrogate cells for scarred VFF.In vitro.Normal VFF cell lines from a 21-year-old male (N21), 59-year-old female (N59), and a scar VFF cell line from a 56-year-old female (S56) were used in this study. 10 ng/mL of transforming growth factor (TGF?1) was applied for 5 days to normal VFF. Myofibroblast differentiation was determined with immunocytochemistry and western blot, measuring alpha smooth muscle actin (?-SMA). Cell growth, proliferation, contractile properties, and gene expression profiles were evaluated.N21, N59, and S56 VFF presented elongated configuration. N21+ and N21- VFF demonstrated significantly greater proliferation compared to N59+, N59-, and S56 VFF at 6 days. ?-SMA was expressed in all cells. Fibronectin, alpha smooth actin, connective tissue growth factor, and metallopeptidase inhibitor were the highest genes expression in VFF treated with transforming growth factor ?1 (TGF?1). At 24 hours, S56 VFF showed lower contraction compared to N21+ and N59+ VFF, but at 60 hours S56 VFF had lower collagen contraction compared to all cell groups. Highest collagen contraction matrices were measured with VFF treated with TGF?1 at 24 hours and N59- VFF at 60 hours.VFF treated with TGF?1 (myofibroblasts) appear to have similar phenotypic characteristics but different genotypic behavior compared to scar VFF.N/A. Laryngoscope, 126:E110-E117, 2016.

SUBMITTER: Branco A

PROVIDER: S-EPMC4755903 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Vocal fold myofibroblast profile of scarring.

Branco Anete A Bartley Stephanie M SM King Suzanne N SN Jetté Marie E ME Thibeault Susan L SL

The Laryngoscope 20150907 3

<h4>Objectives/hypothesis</h4>Vocal fold fibroblasts (VFF) are responsible for extracellular matrix synthesis supporting lamina propria in normal and diseased conditions. When tissue is injured, VFF become activated and differentiate into myofibroblasts to facilitate wound healing response. We investigated if vocal fold myofibroblasts can be utilized as surrogate cells for scarred VFF.<h4>Study design</h4>In vitro.<h4>Methods</h4>Normal VFF cell lines from a 21-year-old male (N21), 59-year-old f ...[more]

PMID: 26344050

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Project description:BackgroundThere is growing interest to application of regenerative medicine approaches in otorhinolaryngological practice, especially in the framework of the therapy of vocal fold (VF) scar lesions. The used conservative and surgical methods, despite the achieved positive outcomes, are frequently unpredictable and do not result in the restoration of the VF's lamina propria's structure, which provides the mechanical properties necessary for vibration. In this connection, the aim of this study was to ascertain the safety and efficacy of a bioequivalent in the treatment of VF scars using a rabbit model of chronic damage.MethodsThe bioequivalent consisted of a hydrogel system based on a PEG-fibrin conjugate and human bone marrow-derived MSC. It was characterized and implanted heterotopically into rats and orthotopically into rabbits after VF scar excision.ResultsWe showed that the fabricated bioequivalent consisted of viable cells retaining their metabolic and proliferative activity. While being implanted heterotopically, it had induced the low inflammatory reaction in 7 days and was well tolerated. The orthotopic implantation showed that the gel application was characterized by a lower hemorrhage intensity (p = 0.03945). The intensity of stridor and respiratory rate between the groups in total and between separate groups had no statistically significant difference (p = 0.96 and p = 1; p = 0.9593 and p = 0.97…1, respectively). In 3 days post-implantation, MSC were detected only in the tissues closely surrounding the VF defect. The bioequivalent injection caused that the scar collagen fibers were packed looser and more frequently mutually parallel that is inherent in the native tissue (p = 0.018). In all experimental groups, the fibrous tissue's ingrowth in the adjacent exterior muscle tissue was observed; however, in Group 4 (PEG-Fibrin + MSC), it was much less pronounced than it was in Group 1 (normal saline) (p = 0.008). The difference between the thicknesses of the lamina propria in the control group and in Group 4 was not revealed to be statistically significant (p = 0.995). The Young's modulus of the VF after the bioequivalent implantation (1.15 ± 0.25 kPa) did not statistically significantly differ from the intact VF modulus (1.17 ± 0.45 kPa); therefore, the tissue properties in this group more closely resembled the intact VF.ConclusionsThe developed bioequivalent showed to be biocompatible and highly efficient in the restoration of VF's tissue.

Project description:Gel-based injectable biomaterials have significant potential for treating vocal fold defects such as scarring. An ideal injectable for vocal fold lamina propria restoration should mimic the microenvironment of the lamina propria to induce scarless wound healing and functional tissue regeneration. Most current synthetic or natural injectable biomaterials do not possess the same level of complex, tissue-specific constituents as the natural vocal fold lamina propria. In this study we present a newly-developed injectable gel fabricated from decellularized bovine vocal fold lamina propria. Blyscan assay and mass spectrometry indicated that the vocal fold-specific gel contained a large amount of sulfated glycosaminoglycans and over 250 proteins. Gene Ontology overrepresentation analysis revealed that the proteins in the gel dominantly promote antifibrotic biological process. In vivo study using a rabbit vocal fold injury model showed that the injectable gel significantly reduced collagen density and decreased tissue contraction of the lamina propria in vocal folds with chronic scarring. Furthermore, this acellular gel only elicited minimal humoral immune response after injection. Our findings suggested that the tissue-specific, injectable extracellular matrix gel could be a promising biomaterial for treating vocal fold scarring, even after the formation of mature scar. STATEMENT OF SIGNIFICANCE: Vocal fold lamina propria scarring remains among the foremost therapeutic challenges in the management of patients with voice disorders. Surgical excision of scar may cause secondary scarring and yield inconsistent results. The present study reports an extracellular matrix-derived biomaterial that demonstrated antifibrotic effect on chronic scarring in vocal fold lamina propria. Its injectability minimizes the invasiveness of the delivery procedure and the degree of mucosal violation. In this work we also describe a new methodology which can more accurately identify proteins from the complex mixture of an acellular extracellular matrix gel by excluding interfering peptides produced during the enzymatic digestion in gel fabrication.

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Vocal fold myofibroblast profile of scarring.

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Vocal fold myofibroblast profile of scarring.

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