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Engineered Vocal Cord Tissue Could Help Treat Voice Disorders

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Lab-grown tissues are a step toward repairing vocal folds damaged by cancer, surgery, or severe overuse. | Flickr/ David Martyn Hunt/ CC BY 2.0

Researchers have recreated human vocal cord tissue that was able to produce sound when transplanted into intact voice boxes from animals. This feat of tissue engineering paves the way to implants capable of replacing damaged vocal cords in patients with voice disorders.

The study appears in the 18 November issue of Science Translational Medicine.

"We never imagined we would see the impressive level of function that we did, and that this engineered tissue created with actual human vocal fold cells would have such strong potential as a therapy," said senior author Nathan Welham, from the University of Wisconsin School of Medicine and Public Health, in a press teleconference on 17 November.

While longer-term studies need to be conducted before the tissue can be ready for the clinic, "it may potentially be an 'off-the-shelf' therapy suitable for use in a variety of patients," said Matthew Brown from the University of Wisconsin-Madison.

Vocal folds, commonly known as vocal cords, within the larynx consist of two flexible bands of muscle lined with delicate tissue called mucosa that vibrate hundreds of times per second to produce sound.

Unlike other tissues in the body which heal after an injury, vocal fold mucosa scars and stiffens, leading to voice impairment. The disorder, called dysphonia, affects about 20 million people in the U.S. alone. Damage to vocal folds, or the nerves that feed into them, can result from cancer surgery, stroke, or other injury.

The few treatments available include injecting synthetic biomaterial or transplanting oral mucosa, the tissue lining inside of the mouth, into the larynx in an attempt to repair damage. Neither is able to fully imitate the highly specialized vocal fold tissue.

One of the biggest challenges in tissue engineering is that fresh human vocal fold cells are difficult to obtain. Taking a biopsy from a healthy individual may easily cause permanent damage.

 
Human vocal cords, here viewed with the help of a strobe light, vibrate hundreds of times each second to create speech and song. | Nathan Welham, University of Wisconsin-Madison

The researchers used two types of healthy vocal fold cells from surgical patients who had their larynges removed for unrelated reasons, and from a cadaver.

When grown in a dish that mimics conditions in the body, the two cell types assembled into three-dimensional layers that closely resembled the structure and protein makeup of natural vocal cord mucosa. Complete vocal fold tissues formed within 14 days.

The cells were "thriving [and] 'talking' to each other," said Brian Frey, also from the University of Wisconsin-Madison. "I think that this tissue engineering is just amazing because the biological system does most of the work. We just have to use the correct cells and give them the right environment to do their job."

When transplanted into excised dog larynges, which are anatomically similar to those in humans, the engineered tissue vibrated in response to air flow and generated sound much like natural tissue. The vocal fold mucosa implant performed better in the dog larynges than an oral mucosa graft, the current standard surgical treatment for voice disorders.

The implant was well-tolerated for up to three months in mice harboring a human immune system, showing that the tissue can be transplanted without being rejected by the body.

The researchers were able to grow about 170 vocal folds using the cells donated from just five individuals, said Welham. "We can make many, many engineered vocal folds from one starting donor," he said, "so that's another advantage of scale when using this approach."

In the future, donated human vocal fold cells might be readily available from tissue banks. It might then be possible to grow large quantities of vocal fold tissue, store them, and have them ready off the shelf for transplantation into a patient. "Those are things that would be investigated as this thing moves kind of closer to clinical trial," said Welham.