University of Wisconsin–Madison

Using stem cells to develop vocal folds in a dish

headshot of Susan Thibeault
Susan Thibeault, PhD, CCC-SLP

A team of researchers, led by Susan Thibeault, PhD, CCC-SLP, have created an in vitro 3-D model of human vocal fold tissue (called mucosa) that could improve our understanding and treatment of disorders affecting the human voice.

The results of the research, published in the journal Nature Communications, remove one of the challenges that has delayed the development of new therapies for laryngeal disease: the lack of a reliable model that researchers could use to study pathological changes in the human voice.

“We have developed a framework for developing clinically useful VF tissue that can not only be used to model the mechanisms that cause a variety of voice disorders, but that can be used to test potential genetic and pharmacological therapies as well,” said Thibeault, professor of surgery, biomedical engineering and communicative disorders in our Division of Otolaryngology. “In addition to the clinical and pharmacological applications, our results bring us an important step closer to one day being able to bioengineer vocal fold tissue for organ replacement.”

The Thibeault lab studies vocal fold injury and wound healing.

Thibeault and her colleagues built on their previous research in mice by showing that vocal-fold epithelia can be derived from human induced pluripotent stem cells (hiPSC). The authors show that the hiPSC-derived vocal fold tissue is genetically and morphologically similar to native human vocal fold mucosa. To test the clinical relevance of their model, they exposed their tissue to a five-percent cigarette smoke extract for one week to see if they could induce the inflammation in the mucosa that is typically associated with smoking. They found that the smoke extract caused mucosal inflammation and induced cellular abnormalities characteristic of damage caused by cigarette use, affecting the epithelial barrier structure.

The vocal folds are the basis of our voice, but they are also essential for separating acoustic communication from the passage of food and drink to the digestive tract and preventing the entry of substances into the respiratory tract. Vocal folds are susceptible to chronic inflammation, mainly caused by environmental insults (including smoke, allergens or infections). However, it is difficult to study vocal diseases and repair strategies because retrieving cell samples from healthy vocal cords could cause irreversible damage.

Treating disorders of the larynx is associated with substantial and far-ranging social, psychological, and economic costs exceeding $11 billion per year, similar to costs associated with asthma, heart disease and depression.

Other UW School of Medicine and Public Health researchers on the study include Vlasta Lungova and Xia Chen, both with the Department of Surgery; and Christina Kendziorski, Department of Biostatistics and Medical Information. The study was funded by the following grants from the National Institute on Deafness and Other Communication Disorders (NIDCD), part of the National Institutes of Health (NIH):  R01DC004336; R01DC012773; and R01 DC014461.

A copy of the full study is available at www.nature.com/articles/s41467-019-12069-w