Derivation of Three-Dimensional Human Induced Pluripotent Stem Cell-Derived Vocal Fold Mucosa for Clinical and Pharmacological Applications

三维人类诱导性多能干细胞衍生的声带粘膜的衍生及其临床和药理应用

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作者:Vlasta Lungova, Susan L Thibeault

Abstract

Healthy vocal fold mucosa is composed of two major cell types, non-keratinized stratified squamous epithelium and vocal fold fibroblasts. Although dysfunction of the epithelium may play a significant pathogenic role in vocal fold diseases, studies at the genetic and molecular level using primary epithelial cells or models of human vocal fold mucosa have been significantly limited by the availability of relevant tissue types, poor growth, and heterogeneity of primary vocal fold epithelial cells. Here, we describe in vitro developmental differentiation of human induced pluripotent stem cells into vocal fold basal epithelial progenitors that were reseeded on collagen-fibroblast constructs to induce stratification and generate a three-dimensional model of human vocal fold mucosa. The engineered vocal fold mucosa represents physiologically relevant and clinically useful model that can be used as a tool for disease modeling and testing of therapeutic approaches for the treatment of laryngeal and VF inflammation.

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