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

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Abstract

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, α-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.

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Acknowledgements

We thank Dr. F. Alipour for help with laryngeal dissection, Erin Ostrem, Jon Aanestad, and Doug Havel for their assistance, Katherine Walters (Senior Research Assistant, Central Microscopy Research Facility of the University of Iowa) for help with microscopy, Kelvin Lehrman for image digitization, and Dr. S. Thibeault for her gift of the tracheal fibroblasts.

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Authors and Affiliations

  1. National Center for Voice and Speech, Department of Speech Pathology and Audiology, University of Iowa, 330 Wendell Johnson Speech and Hearing Center, IA 52242, Iowa City, USA

    Tannin J. Fuja, Megan N. Probst-Fuja & Ingo R. Titze

  2. National Center for Voice and Speech, The Denver Center for the Performing Arts, CO 80204, Denver, USA

    Ingo R. Titze

Authors
  1. Tannin J. Fuja
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  2. Megan N. Probst-Fuja
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  3. Ingo R. Titze
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Corresponding author

Correspondence to Tannin J. Fuja.

Additional information

This research was supported by grants from the NIDCD/NIH (grant nos. R01DC004347 and R01DC004224).

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Fuja, T.J., Probst-Fuja, M.N. & Titze, I.R. Transdifferentiation of vocal-fold stellate cells and all-trans retinol-induced deactivation. Cell Tissue Res 322, 417–424 (2005). https://doi.org/10.1007/s00441-005-0028-9

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  • DOI: https://doi.org/10.1007/s00441-005-0028-9

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