In an experimental first, scientists reported Wednesday that they have grown about 170 human vocal cords in a lab, starting from cells taken from four surgical patients and one cadaver.
About 20 million Americans have vocal cord injuries, and they’ve plagued some of the world's most famous singers, including Julie Andrews, Adele, and John Mayer. The new medical engineering feat is a first step in developing better treatments for the worst of these cases.
Preliminary animal experiments suggest the lab-grown voice boxes will perform like real ones, unlike current repairs for damaged vocal cords, the scientists reported in the journal Science Translational Medicine. And the lab-grown vocal cords didn’t require immune system drugs, unlike most other transplant tissues.
“We never imagined that we would see the impressive level of function that we did,” said study senior author Nathan Welham of the University of Wisconsin Medical School at a briefing for reporters.
Although it’s still very early, Welham and his colleagues envision someday growing new voice boxes for people with the most severe scarring, and then implanting them surgically. Smaller vocal cord scars could be patched with the lab-grown tissues.
“What makes this tremendously exciting is that we just don’t have great treatments for these people,” Seth Cohen, a head and neck surgeon at Duke University who was not part of the study team, told BuzzFeed News. “You don’t miss your voice until it is gone, and then you really miss it. People cannot work and they suffer tremendous isolation.”
In the study, the team implanted their lab-grown vocal cords into the kidneys of mice genetically engineered to possess a human immune system. (Why kidneys? “We had to,” Welham said. “Their larynx is way too small.”) The tissues grafted without need of transplant drugs.
“This is not too surprising. The larynx has to be tolerant of everything we eat and breathe,” Jennifer Long, a otolaryngologist at UCLA who was not part of the study, told BuzzFeed News. But the immune system tolerance makes the prospect of transplants of lab-grown vocal cords much more appealing, she added. “You don’t want swelling from an immune reaction in your windpipe.”
The study team also attached the voice tissues to the removed larynxes of two laboratory dogs (ones donated from other research, not killed for the experiments), placed them in a plastic tube designed to mimic the human windpipe, and blew wind through them, mimicking exhalations to produce tones very close to natural voice boxes.
“It sounded like a kazoo,” Welham said. “An ‘eeeee’ noise.”
Perched atop the windpipe, the voice box serves as a noise-maker for speech and song.
Vocal cords are less than an inch tall, twin folds of skin and muscle. (The supple but tough surface is similar to the skin on the inside of the mouth, but stronger.) The two cords vibrate together some 100 to 1,000 times per second, and generate the tones that your throat turns into voice or song.
“It’s pretty remarkable that our speech starts this way, kind of a buzz at the base of the throat,” Long said. Injuries from cysts, infections, cancer, or overuse can scar the vocal cords, leading to permanent hoarseness or, in the worst cases, loss of speech.
Current treatments for the worst vocal cord damage don’t deliver great outcomes, Long said, due to the persistence of scars. (Julie Andrews actually lost her full singing voice in 1997 after an operation to remove nodules from her vocal cords.)
At first, the researchers were only interested in learning how vocal cord tissue grew. They collected cells from four human surgery patients and one dead medical donor, and grew them on a collagen scaffold.
Much to their surprise, these cells naturally and quickly developed over just 14 days into folds of voice box tissue. They grew so well that only a few cells were enough to create more than 100 vocal cords, Welham said, “and we have cells left over.”
“This is tissue engineering where the biology does most of the work,” study co-author Brian Frey of the University of Wisconsin, Madison, said. “We just have to give the correct cells the right environment to do their jobs.”
If the immune system tolerance of the substitute vocal cords proves true in longer-lived mice with human immune systems, the team foresees experiments with full-scale larynx transplants in larger animals in the next few years.
The FDA treats implants of cells as biological therapies requiring extensive animal data before they can be tested in people, Welham noted. The first human experiments would probably be done on people who can't speak at all.
“For the most severe cases," Long said, "you could see this as the kind of transplant option we have been looking for."