January 7, 2021

Regenerating the larynx: A second chance at speech

By Susan Buckles

Mayo Clinic is leveraging advances in regenerative medicine to restore function for people whose lives have been drastically changed by a laryngectomy — surgery to remove the voice box. People without a voice box can neither speak with their natural voices nor breathe through their noses. Simple pleasures like smelling a bouquet of flowers or tasting favorite foods are greatly diminished, if not impossible. Mayo Clinic's Center for Regenerative Medicine invests in innovation to develop new ways to regenerate the voice box and restore normal abilities after diseases of the larynx.

David Lott, M.D.

"Until recently, there was no way to restore function when a larynx was removed. Some people would choose to live a shorter life rather than suffer with physical deficits left after a laryngectomy," says David Lott, M.D., an ear, nose and throat specialist and associate director of Center for Regenerative Medicine in Arizona.

As many as 60,000 people in the U.S. are living without a voice box, mostly due to laryngeal cancer or the residual effects of radiation damage. Others have irreversible traumatic injury to their larynx. The need for new therapies is great, with 12,000 new cases of laryngeal cancer diagnosed every year, according to the National Cancer Institute.

After a laryngectomy, the patient must breathe through a hole in the neck called a tracheostoma. That can be socially embarrassing and physically challenging. For instance, even taking a shower could be a drowning risk if water got into the opening in the neck. Then there's the arduous task of relearning to speak. Many people without a voice box use a prosthesis that allows them to make sounds by pushing air from the lungs through a valve. Another option for speaking is a battery-operated device that, when held to the throat, makes a mechanical robotic sound.

Mayo Clinic is pioneering three approaches for repairing the larynx that have potential to regenerate form and function in this complex organ.

Larynx transplantation

Advances in microsurgery have positioned Mayo Clinic to be among the first to offer larynx transplantation. Using powerful microscopes, surgeons are able to connect tiny blood vessels and nerves to successfully transplant a larynx from a deceased donor to a live patient. The United Network for Organ Sharing has granted the Mayo Clinic Larynx and Trachea Transplant Program in Arizona permission to perform these transplants. United Network for Organ Sharing is the federally-designated program that manages the nation’s organ transplant system. Mayo Clinic will perform two larynx transplants per year for the next five years through a first-of-its-kind clinical trial, after which the results will be evaluated for use in standard clinical care.

Transplantation is most suitable for people with larynx injury or those who have been cured from laryngeal cancer, but either have had a laryngectomy or radiation damage that hampers their ability to eat, speak and breathe.

"A larynx transplant would bring in all nice, new healthy tissue. A successful larynx transplant could restore the patient’s ability to breathe through their nose, swallow normally and speak with a more natural sounding voice," says Dr. Lott.   

A larynx transplant offers the most promising way to recover laryngeal function, but it comes with a tradeoff. After the transplant, the patient will require lifelong immunosuppressants to prevent organ rejection.

3D printed implants

Oftentimes, laryngeal cancer affects only half of the voice box. Mayo Clinic has discovered a new way to remove just the diseased portion of the larynx while preserving the healthy part. Using CT scans, Mayo Clinic is able to create a 3D replica of the diseased portion of the larynx with exact dimensions of the section that was removed. The 3D scaffold is printed and implanted within the larynx.

"This could prevent the need for a laryngectomy, thereby preventing the need for a transplant. Patients would not need the tracheostomy tube in the long term. They could eat and drink like normal and retain a natural voice," says Dr. Lott 

After the scaffold is implanted, Richard Hayden, M.D., a fellow ear, nose and throat specialist, uses a muscle flap to cover the implant. Over time, soft tissue grows into the scaffold, regenerating the portion of the voice box lost to cancer. The procedure is expected to last throughout the patient’s life. The implanted scaffold is currently available in clinical care.

Dr. Lott’s research seeks to further advance 3D printed implants. His team is investigating whether the use of stem cells and growth factors seeded within the 3D scaffold would regenerate larynx tissue without the need for muscle flap surgery.

"Using stem cells and other growth factors allows the body to form a natural epithelial lining. Our theory is that we would not need to use muscle from other parts of the body to complete the surgery. That could save healing time and money for the patient. They may not need a tracheostomy after surgery," says Dr. Lott.  

Dr. Lott hopes to advance his research with the 3D stem cell implants from the current preclinical studies to human clinical trials by 2022. In the meantime, his team seeks to identify the first candidates for larynx transplantation in 2021.

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Tags: #Dr. David Lott, #Dr. Richard Hayden, #laryngeal cancer, #laryngectomy, #Larynx transplantation, #Mayo Clinic Center for Regenerative Medicine, #medical research, #Regenerative medicine, 3D Printing, Cancer, Practice, Research

Hello would your implants work to repair damaged voice box tissue? I ask because I had LPR for a long time which damaged the back of my voice box making it difficult to eat and breath.

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Unfortunately, this specific research is not designed to help that sort of a problem.

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Is there research being done with stem cells and bilateral vocal cord paralysis?

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Hi my name is Stephen. I had a total Laryngectomy surgery. Can this research help me

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@stevewinchesterspw

Hi my name is Stephen. I had a total Laryngectomy surgery. Can this research help me

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Unfortunately, Dr. Lott says, "The tissue engineered larynx is not an option for people who have had a laryngectomy already. We do have a laryngeal transplant program running. It is designed to ultimately help people who have already had a laryngectomy. However, it will be a few years before it is available to those patients."

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@susanbuckles

Unfortunately, Dr. Lott says, "The tissue engineered larynx is not an option for people who have had a laryngectomy already. We do have a laryngeal transplant program running. It is designed to ultimately help people who have already had a laryngectomy. However, it will be a few years before it is available to those patients."

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Please keep informed of new developments on Laryngeal transplants. I will appreciate the info

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I had a total laryngectomy due to papillary thyroid cancer (the good one, ha) 12/30/15. I breathe through a stoma, not through my mouth or nose, and I speak with an electrolarynx. I'm confused because in one area it sounds like I would be a candidate for the larynx transplant and two a year are being done, but then in the comments, the program will not be available for a few years? Please confirm. Am I missing something? Obviously, people like me would be very interested in being able to breathe and speak as close to normal as possible. I am very interested in this program and hope it's available closer than a few years.

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@lsmith98

I had a total laryngectomy due to papillary thyroid cancer (the good one, ha) 12/30/15. I breathe through a stoma, not through my mouth or nose, and I speak with an electrolarynx. I'm confused because in one area it sounds like I would be a candidate for the larynx transplant and two a year are being done, but then in the comments, the program will not be available for a few years? Please confirm. Am I missing something? Obviously, people like me would be very interested in being able to breathe and speak as close to normal as possible. I am very interested in this program and hope it's available closer than a few years.

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Dr. Lott says, "The trial is running now but we don’t anticipate opening it to current laryngectomy patients for a few years. That patient population is more difficult since it might be challenging to find the blood vessels and nerves once they have already had a laryngctomy."

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Hi the thought that maybe I will be around to be able to get a larynx transplant excites me. I too would like to be informed of all new updates on this and if I am not a chosen candidate I hope someone will find something that can help us not to walk around with a hole in our throats maybe hidden in our chest area and something more inventive than a large button that makes everyone sound like a man . Please don't mistake my frustration for ungratefulness but there has to be a better way so we don't get the pitiful stares Thank you for listening

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@boyds

Is there research being done with stem cells and bilateral vocal cord paralysis?

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Not for stem cells and bilateral vocal cord paralysis. There are other research studies on vocal fold paralysis that are not yet FDA approved, but hope they will be soon.

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