Many of us have experienced voice trouble — a nasty cough, shouting at a concert
But lo and behold, science is finding a way to help. On Wednesday, an international team of scientists announced they have recreated human vocal cord tissue in a dish that, when transplanted into the intact voice boxes of dogs, can create sound. In the future, it’s likely these engineered tissues will be grown outside of the body, ready to be transplanted into a patient.
“Regenerative medicine therapy such as the engineered vocal fold tissues has this potential to significantly alleviate suffering,” said Matthew Brown, a coauthor of the recent paper, in a press conference Tuesday. “We believe this tissue is a promising therapeutic candidate that has the potential to restore vocal function in patients who have lost their voice.”
People with voice impairment due to tissue loss or vocal fold fibrosis have few treatment options. The sort of tissue here isn’t like other tissues in the body that heal after injury; the scars of vocal fold mucosa injury stiffen, resulting in voice loss. The team behind the most recent research realized what was needed was a transplantable, bioengineered vocal fold mucosa — tissue that is capable of aerodynamic-to-acoustic energy, high frequency vibration, and is physiologically capable of maintaining a barrier against the airway lumen.
“An ideal replacement tissue for the vocal fold has to satisfy stringent demands,” said co-author Dr. Nathan Welhman at a press conference. “It must be strong enough to withstand rapid acceleration, deceleration, and repeated impact stress at vibration rates up to 1,000 times per second. There is no other tissue in the human body that is subject to these types of biochemical demands.”
To solve this problem they bioengineered vocal fold mucosa from healthy vocal fold cells from two surgical patients, and from one cadaver. Once functional mucosa was created from vocal fold cells, it was grafted into a cadaver dog larynx (voice box) — which are anatomically similar to a human’s larynx. These were then grafted into mice that were implemented with a human immune system.
And it worked — the mice were able to tolerate the vocal fold implants for up to three months.
“At the outset we never imagined that we would see the impressive level of function that we did,” said Welham.
Looking to the future, the research team wants to find what happens exactly after the tissues are implanted. Biology, says co-author Dr. Brian Fry, does most of the work.
“We have to use correct cells and give them the right environment to do their job,” said Fry at Tuesday’s press conference. “The hope is that they will continue to do their job once the engineered vocal fold is implanted into a person.”
“Our goal is to understand what is happening as engineered vocal fold tissues are being remodeled in a living animal and to use this to improve the tissue engineering process.”
Immediate next steps include preparing for a different humanized mouse model that will allow for longer-term examination that will demonstrate whether it will be tolerated by the immune system over a long period of time and if it will keep its physiologic force production properties. While the team has created human sized vocal folds, actual clinical trials on people are a ways away.
When the procedure is ready for humans, Welham envisions a future where the tissue is prepared for the patient in a 14-day in-lab process. He foresees two potential scenarios for the actual implementation.
“One is we schedule a procedure and in 14 days ahead of that, we defrost cells and start engineering the tissue so that it’s ready for placement in surgery,” said Welham. “The other alternative is to generate them and store them at the finished point, and see if they are able to be stored and kept for off-the-shelf placement.”
Lab-grown, transplantable vocal tissue ready for the taking. Now that’s something to sing about.