Transdifferentiation of vocal-fold stellate cells and all-trans retinol-induced deactivation

The maculae flavae of the human vocal folds include dense extracellular matrices and compacted cells with a stellate morphology. These vocal-fold stellate cells are thought to participate in the metabolism of extracellular matrices essential in maintaining vocal-fold viscoelasticity required for phonation. We have isolated and cultured these new cells and have tested the hypothesis that they maintain a distinct cellular and biochemical phenotype. We have compared proliferation rates, changes on immunophenotype, and intracellular lipid and vitamin A storage. Vocal-fold stellate cells undergo culture-induced transdifferentiation to a myofibroblast-like phenotype with an altered phenotype resembling, but not identical to, activated hepatic and pancreatic stellate cells. Our results reveal that these cells are capable of responding to exogenous all-trans retinol in culture. Exposure to this synthetic co-factor causes deactivation characterized by decreased proliferation, loss of the activated stellate cell marker, alpha-smooth muscle actin, and restoration of intracellular lipid and vitamin A metabolite storage. These data establish a new and distinct cellular target for future investigations of the viscoelastic properties of the vocal-fold mucosa during normal phonation, aging, vocal-fold scarring, laryngeal fibrosis, and myofibroblastoma.