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In vitro evaluation of anti-fibrotic effects of select cytokines for vocal fold scar treatment.

ABSTRACT: Scarring of the vocal fold lamina propria (LP) can cause considerable voice disorders due to reduced pliability in scar tissue, attributed in part to abnormal extracellular matrix (ECM) deposition produced by the fibrotic vocal fold fibroblast (fVFF). Cytokines with anti-fibrotic potential have been investigated to limit abnormal LP ECM, but are limited by the need for repeat injections. Moreover, the potentially significant role played by activated macrophages (AMOs) is usually not considered even though the interaction between AMO and fibrotic fibroblasts is known to regulate scar formation across different tissues. AMO are also regulated by cytokines that are used for LP scar removal, but little is known about AMO behaviors in response to these cytokines within the context of LP scar. In the present study, we evaluated anti-fibrotic effects of hepatocyte growth factor (HGF), interleukin-10 (IL-10) and interleukin-6 (IL-6) in a 3D, in vitro fVFF-AMO co-culture system using poly(ethylene glycol) diacrylate (PEGDA) hydrogels. Data from all cytokines was synthesized into a heat-map that enabled assessment of specific associations between AMO and fVFF phenotypes. Cumulatively, our results indicated that both HGF and IL-10 are potentially anti-fibrotic (reduction in fibrotic markers and enhancement in normal, anti-fibrotic VFF markers), while IL-6 displays more complex, marker specific effects. Possible associations between AMO and fVFF phenotypes were found and may highlight a potential desirable macrophage phenotype. These data support the therapeutic potential of HGF and IL-10 for LP scar treatment, and shed light on future strategies aimed at targeting specific AMO phenotypes. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1056-1067, 2019.

SUBMITTER: Chen H

PROVIDER: S-EPMC7011756 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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In vitro evaluation of anti-fibrotic effects of select cytokines for vocal fold scar treatment.

Chen Hongyu H Erndt-Marino Josh J Diaz-Rodriguez Patricia P Kulwatno Jonathan J Jimenez-Vergara Andrea C AC Thibeault Susan L SL Hahn Mariah S MS

Journal of biomedical materials research. Part B, Applied biomaterials 20180905 4

Scarring of the vocal fold lamina propria (LP) can cause considerable voice disorders due to reduced pliability in scar tissue, attributed in part to abnormal extracellular matrix (ECM) deposition produced by the fibrotic vocal fold fibroblast (fVFF). Cytokines with anti-fibrotic potential have been investigated to limit abnormal LP ECM, but are limited by the need for repeat injections. Moreover, the potentially significant role played by activated macrophages (AMOs) is usually not considered e ...[more]

PMID: 30184328

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Project description:Candidate cell sources for vocal fold scar treatment include mesenchymal stromal cells from bone marrow (BM-MSC) and adipose tissue (AT-MSC). Mechanosensitivity of MSC can alter highly relevant aspects of their behavior, yet virtually nothing is known about how MSC might respond to the dynamic mechanical environment of the larynx. Our objective was to evaluate MSC as a potential cell source for vocal fold tissue engineering in a mechanically relevant context. A vibratory strain bioreactor and cDNA microarray were used to evaluate the similarity of AT-MSC and BM-MSC to the native cell source, vocal fold fibroblasts (VFF). Posterior probabilities for each of the microarray transcripts fitting into specific expression patterns were calculated, and the data were analyzed for Gene Ontology (GO) enrichment. Significant wound healing and cell differentiation GO terms are reported. In addition, proliferation and apoptosis were evaluated with immunohistochemistry. Results revealed that VFF shared more GO terms related to epithelial development, extracellular matrix (ECM) remodeling, growth factor activity, and immune response with BM-MSC than with AT-MSC. Similarity in glycosaminoglycan and proteoglycan activity dominated the ECM analysis. Analysis of GO terms relating to MSC differentiation toward osteogenic, adipogenic, and chondrogenic lineages revealed that BM-MSC expressed fewer osteogenesis GO terms in the vibrated and scaffold-only conditions compared to polystyrene. We did not evaluate if vibrated BM-MSC recover osteogenic expression markers when returned to polystyrene culture. Immunostaining for Ki67 and cleaved caspase 3 did not vary with cell type or mechanical condition. We conclude that VFF may have a more similar wound healing capacity to BM-MSC than to AT-MSC in response to short-term vibratory strain. Furthermore, BM-MSC appear to lose osteogenic potential in the vibrated and scaffold-only conditions compared to polystyrene, potentially attenuating the risk of osteogenesis for in vivo applications.

Dataset Information

In vitro evaluation of anti-fibrotic effects of select cytokines for vocal fold scar treatment.

Publications

In vitro evaluation of anti-fibrotic effects of select cytokines for vocal fold scar treatment.

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