John Maniaci
Dr. Nathan Welham led a team of UW scientists that has grown vocal folds, which one day may help restore voices.
Dr. Seth Dailey knows it’s hard to underestimate the power of voice.
“Think about the number of people you make judgments about based on their voice,” says Dailey, a UW-Madison surgeon who specializes in vocal disorders. “We do it all the time. It’s part of the perceptual package. It affects how people can do their jobs with altered voice production. Vocal issues are more important than ever before in human history.”
The ability to speak has almost become an economic imperative, he adds. “We live in a society that has changed from largely agrarian to industrial to communication-based,” says Dailey. “Nowadays about two-thirds of the workforce relies on good voice communication.”
People with voice impairments can look forward to an upgrade now that UW scientists have succeeded in growing functional vocal cord tissue in the laboratory.
The work was spearheaded by Dr. Nathan Welham, a speech-language pathologist, who assembled a team of UW scientists knowledgeable about the biochemical pathways and physiology of vocal tissue, its physical properties and the likely immune response.
“Some of my patients have really challenging voice difficulties that we can’t treat because the vocal cord is too severely damaged to be fixed or has been removed because of a lesion or tumor,” Welham says.
The team has been exploring ways to regenerate or create new vocal cords, more accurately called vocal folds, that could restore voice quality.
It has taken more than six years to get this far. Welham needed to obtain normal, healthy vocal tissue, because the cells of the vocal fold are very specialized. No other tissue in the body needs to vibrate hundreds of times a second.
“We can’t take a sample from a healthy person,” Welham says. “That would create an injury leading to scarring and could result in a voice problem for the donor.” But there are challenges getting cells quickly enough from bodies donated for research. The only other opportunity to get healthy tissue is the rare case where a person needs to have a healthy voice box removed.
Starting with vocal-fold tissue from a cadaver and four patients who had their larynxes removed, Welham’s team grew the cells. They then applied them to a 3-D collagen scaffold, which is similar to how artificial skin is grown in a laboratory.
In about two weeks, the cells formed a pliable, strong tissue that could transmit sound comparable to normal vocal folds when placed inside a larynx and attached to an artificial windpipe.
The team next tested the new tissue to see if it would be rejected by mice engineered to have human immune systems. No host immune reaction was triggered. The team is optimistic about transplantation into a human host.
“Putting a new vocal fold into someone’s body will not make them sound like a different person,” says Welham. “The sound is modified by the shape of the throat, mouth and nose. Those things won’t change. It’s more like putting a new string on a violin.”
Actual human vocal fold transplants are still years away. “The next logical step is to learn how how these tissues behave when they are inside the body for a long time,” says Welham. “We will need to get permission from the FDA and other regulators to do a trial on humans.”
Dailey is excited about the potential. While people need voices more than ever, vocal cord stress and injury is increasingly common. It’s easy to imagine getting a hockey stick to the front of the neck, but most people are more at risk for a breathing tube injury from the 30 million intubations in the U.S. every year. Cancer, benign tumors of the larynx and vocal cord polyps can also challenge the voice.
“The thing people complain about with vocal cord surface injury is vocal effort,” Dailey says. “The ability to make themselves heard becomes a chore that has consequences of physical fatigue, strain and social isolation — they just won’t bother talking any more, or they will only talk in a quiet environment, or they are completely done in by 3 p.m.”
“What we surgeons have always wanted for people who have been injured is some sort of replacement of the surface,” he adds. “This is the holy grail of our field.”