Dataset Information

Biomechanical Screening of Cell Therapies for Vocal Fold Scar.

ABSTRACT: 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.

SUBMITTER: Bartlett RS

PROVIDER: S-EPMC4555478 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Biomechanical Screening of Cell Therapies for Vocal Fold Scar.

Bartlett Rebecca S RS Gaston Joel D JD Yen Tom Y TY Ye Shuyun S Kendziorski Christina C Thibeault Susan L SL

Tissue engineering. Part A 20150722 17-18

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 cD ...[more]

PMID: 26119510

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Project description:MotivationHuman voice is generated in the larynx by the two oscillating vocal folds. Owing to the limited space and accessibility of the larynx, endoscopic investigation of the actual phonatory process in detail is challenging. Hence the biomechanics of the human phonatory process are still not yet fully understood. Therefore, we adapt a mathematical model of the vocal folds towards vocal fold oscillations to quantify gender and age related differences expressed by computed biomechanical model parameters.MethodsThe vocal fold dynamics are visualized by laryngeal high-speed videoendoscopy (4000 fps). A total of 33 healthy young subjects (16 females, 17 males) and 11 elderly subjects (5 females, 6 males) were recorded. A numerical two-mass model is adapted to the recorded vocal fold oscillations by varying model masses, stiffness and subglottal pressure. For adapting the model towards the recorded vocal fold dynamics, three different optimization algorithms (Nelder-Mead, Particle Swarm Optimization and Simulated Bee Colony) in combination with three cost functions were considered for applicability. Gender differences and age-related kinematic differences reflected by the model parameters were analyzed.Results and conclusionThe biomechanical model in combination with numerical optimization techniques allowed phonatory behavior to be simulated and laryngeal parameters involved to be quantified. All three optimization algorithms showed promising results. However, only one cost function seems to be suitable for this optimization task. The gained model parameters reflect the phonatory biomechanics for men and women well and show quantitative age- and gender-specific differences. The model parameters for younger females and males showed lower subglottal pressures, lower stiffness and higher masses than the corresponding elderly groups. Females exhibited higher subglottal pressures, smaller oscillation masses and larger stiffness than the corresponding similar aged male groups. Optimizing numerical models towards vocal fold oscillations is useful to identify underlying laryngeal components controlling the phonatory process.

Dataset Information

Biomechanical Screening of Cell Therapies for Vocal Fold Scar.

Publications

Biomechanical Screening of Cell Therapies for Vocal Fold Scar.

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