Fresh Voices: Researchers Grow New Vocal Cords From Cells

Researchers say they’ve grown new sets of vocal cords from just a few cells, and think they might be able to create custom-grown replacements for people who have lost their own voices.

The highly specialized cells — taken from living people and from a cadaver — assembled themselves into the right structure, the team at the University of Wisconsin reported.

And they made a kazoo-like buzzing sound when warm air was blown through them — an indication that they had the right properties needed to create a voice inside a human larynx.

“Part of the advantage of using an engineered tissue is that we can customize the size and make the tissue to fit the defect, and also fit the size of the vocal fold in the male or female or child that would be the recipient,” said Dr. Nathan Welham, who helped lead the research.

As many as 20 million Americans have impaired voices because of damage to the vocal cords — more precisely, vocal folds — the researchers report in the journal Science Translational Medicine. There’s no good solution for them now.

Organs for transplant are always in short supply and no one’s really tried transplanting vocal folds into a living patient, the team said. They decided to try growing new ones.

It’s not an easy thing to do. The tissue that makes up vocal folds is extremely specialized. Not just any old tissue will do the job.

“It must be soft and pliable enough to be set into vibration by an air stream."

“It must be soft and pliable enough to be set into vibration by an air stream, propagate a traveling wave across its surface similar to a wave that moves across a body of water, for example, and also must be strong enough to withstand rapid acceleration and deceleration and repeated impact stress as the tissue vibrates at rates in the hundreds or up to a thousand cycles or a thousand times per second,” Welham told reporters in a telephone briefing.

“There is no other tissue in the human body that is subject to these types of biomechanical demands.”

They got vocal fold tissue from four patients who’d had their larynxes removed for various reasons – not cancer – and from one cadaver. They washed it down to sort out the individual cells and then grew them in solution before seeding them onto a collagen scaffolding.

“We ended up with an engineered tissue in about 14 days,” said Changying Ling, who also worked on the study team.

Some regenerative tissue research is done using stem cells – the immature master cells of the body that are the source of various tissues. In this case, however, they just took cells from vocal folds.

The cells seemed to know what to do, the researchers said. “They're effectively talking to each other and producing the structural proteins that make this special tissue capable of vibration,” Brian Frey, who worked on the project, told reporters.

The team tested their bioengineered vocal folds in larynxes taken from the bodies of dogs that had died. They fit in and vibrated when air was blown through them.

Welham demonstrated, making a buzzing sound. “The voice sounds a little bit like a kazoo, kind of robotic sounding,” he said. “And so you would hear that sound and think, gosh, that sounds kind of synthesized or robotic. That doesn't sound so human, but that's how it should sound in this context.”

Inside a human larynx, it would sound like a voice, he said.

“The voice sounds a little bit like a kazoo, kind of robotic sounding."

Like any transplanted tissue, there’s a risk of an immune system reaction that could damage the transplant or make the patient sick. But early tests in mice suggest that the specialized vocal fold tissue in fact doesn’t stimulate much of an immune response.

That suggests the transplants could be grown ahead of time and frozen, and might not need to be carefully matched to the recipient, Welham said.

“The cells that come from human vocal folds are uniquely suitable to be used for this purpose, but they're not that easy to obtain,” he said. So having them grown ahead of time would be an advantage. And a single donor could provide enough cells for several transplants if there was time to grow them first in the lab.

More work is needed, the researchers stressed. They must test their vocal folds in more animals to see what kind of immune response they generate. And because vocal folds are not necessary for life, they’ll have to pass a higher safety bar to get approved for use in human patients than vital organs such as hearts or lungs.