Identification of distinct layers within the stratified squamous epithelium of the adult human true vocal fold

Abstract

Objectives/Hypothesis A precise molecular schema for classifying the different cell types of the normal human vocal fold epithelium is lacking. We hypothesize that the true vocal fold epithelium has a cellular architecture and organization similar to that of other stratified squamous epithelia including the skin, cornea, oral mucosa, and esophagus. In analogy to disorders of the skin and gastrointestinal tract, a molecular definition of the normal cell types within the human vocal fold epithelium and a description of their geometric relationships should serve as a foundation for characterizing cellular changes associated with metaplasia, dysplasia, and cancer. Study Design Qualitative study with adult human larynges. Methods Histologic sections of normal human laryngeal tissue were analyzed for morphology (hematoxylin and eosin) and immunohistochemical protein expression profile, including cytokeratins (CK13 and CK14), cornified envelope proteins (involucrin), basal cells (NGFR/p75), and proliferation markers (Ki67). Results We demonstrated that three distinct cell strata with unique marker profiles are present within the stratified squamous epithelium of the true vocal fold. We used these definitions to establish that cell proliferation is restricted to certain cell types and layers within the epithelium. These distinct cell types are reproducible across five normal adult larynges. Conclusion We have established that three layers of cells are present within the normal adult stratified squamous epithelium of the true vocal fold. Furthermore, replicating cell populations are largely restricted to the parabasal strata within the epithelium. This delineation of distinct cell populations will facilitate future studies of vocal fold regeneration and cancer. Level of Evidence N/A.

Tissue engineering-based therapeutic strategies for vocal fold repair and regeneration

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Regeneration of Vocal Fold Mucosa Using Tissue-Engineered Structures with Oral Mucosal Cells

“…Immunohistochemical staining was performed with a polyclonal antibody against cytokeratin 8 intermediate filament protein (MyBioSource, San Diego, CA) and a monoclonal antibody against vimentin (Abcam plc, Cambridge, UK). Cytokeratin 8 is expressed in normal oral epithelial cells, but not in vocal fold epithelial cells [ 14 , 15 ]. Vimentin, an intermediate filament protein, is expressed in a large variety of cells, including fibroblasts, endothelial cells, macrophages, neutrophils, and lymphocytes, and serves as an indicator of cell proliferation in wound healing [ 16 ].…”