Vocal Fold Regeneration Gains Voice

Kyoto University

Kyoto, Japan -- The larynx, also known as the voice box, is home to your vocal folds and is the reason you can talk and sing while manipulating the pitch and volume of your voice. The vocal folds, which are part of the larynx, are covered with mucosa, or mucous membranes.

Besides vocalization, the larynx also serves other essential functions such as breathing, airway protection, and swallowing. For this reason, any kind of damage resulting in laryngeal dysfunction, or vocal cord dysfunction, can severely disrupt a person's life and lead to symptoms such as voice disorders, chronic cough, or aspiration.

"Vibration of the vocal fold in the larynx plays a crucial role in voice production," says Japanese researcher Koichi Omori. "However, these tissues are difficult to regenerate after injury or the surgical removal of head or neck tumors, which can significantly affect a patient's quality of life."

Scientists have been exploring regenerative therapies for these conditions, but the efficacy of these treatments remains insufficient. In order to improve such therapies, understanding the mechanisms that maintain tissue homeostasis is crucial, but current knowledge in this area is still limited regarding the larynx.

Motivated to close this treatment gap, a team of researchers from Kyoto University, Kyushu University, and Kumamoto University, led by Omori, set out to elucidate the mechanisms underlying laryngeal tissue maintenance and stem cell regulation.

The team used single-cell RNA sequencing to analyze the laryngeal mucosa in mice. They also performed spatial transcriptomics using photo-isolation chemistry to examine small regions of the vocal fold lamina propria, connective tissue forming part of the mucosa. Additionally, the researchers were able to create in vitro models of organoids from the laryngeal epithelium, a thin layer of protective tissue.

The group's results reveal that multiple types of stromal and secretory cells can be found in different areas of the larynx. In the mouse vocal fold, the researchers were surprised to identify both SOX9-positive basal cells and Lgr5-positive cells in vocal fold lamina propria. Furthermore, they established three types of laryngeal organoids.

This study contributes new insights into the larynx and regenerative medicine, including the provision of laryngeal organoids as a research tool. Next, the team plans to investigate the functions of the SOX9-positive basal cells and Lgr5 cells in vocal fold lamina propria.

"We have been working on regenerative medicine for the larynx and trachea since 2000, and have now identified potential stem cells for the vocal fold mucosa. Building on this discovery, we aim to develop new treatments to help restore lost voices," says Omori.

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