First transplant of a human windpipe reconstructed using stem cells
1 Mar 2011
Professor of laryngology and ear, nose and throat surgeon, University College London
Professor Martin Birchall co-led the pioneering research team which carried out the first transplant of a human windpipe reconstructed using stem cells. Now, MRC funding is helping him to build on this success by developing the first clinical trials of a stem-cell-derived larynx transplant.
Starting out as a head and neck cancer surgeon, Martin spent many years working on conventional tissue transplantation. But he became fascinated by its limitations: the need for patients to take drugs to suppress the immune system, the shortage of tissue donors and the simple fact that some tissues and organs are technically or ethically impossible to transplant.
So Martin’s research interests turned to the possibility of using adult stem cells to engineer tissues. Stem cells have the ability to turn into any type of human cell and because they are extracted from the patient there’s no risk of them being rejected by the immune system.
In 2008, Martin used tissue engineering techniques he and his team had been developing in pigs to partially reconstruct a new trachea (windpipe) for a patient using her own stem cells.
“That was the first time that a transplant an organ built from stem cells had ever been performed in a person and it seemed to work first time. It was a major breakthrough for science and technology,” says Martin.
Restoring the voice
Now, with £1.2m funding from the MRC, Martin is taking this research to the next level. This substantial sum will enable him to take the research from one-off treatments for patients in exceptional circumstances to developing the first clinical trial of tissue-engineered larynx (voicebox) transplants; a project known as RegenVox.
Losing the use of your larynx can be devastating – it not only affects speech, swallowing and breathing, but also sense of smell and the ability to cough or even to kiss. Scientists working on the project will use stem cells to partially re-build the larynx and restore its function, potentially helping over a thousand patients each year with serious larynx problems.
The procedure involves taking stem cells from the patient, such as those found in bone marrow. In the laboratory, the stem cells are coaxed to differentiate into cells of the desired type by exposing them to the chemical signals to which they’d normally respond inside the body. To encourage the cells to form into the shape of a trachea or larynx, the team seed the cells onto a framework made of collagen, a connective tissue protein found throughout the human body that defines its form and structure, or onto a nanocomposite (synthetic) scaffold.
Alongside the newly-made cells, the team also mix in some of the original stem cells to form the blood vessels and other supporting tissues.
“Having found themselves in certain environments a stem cell will look around and say ‘This has got the correct feel to it, the right stimuli, shape of a muscle, a piece of cartilage, a piece of bone’ and will therefore differentiate in those ways. So, for example, if it’s an environment with lots of other cartilage cells it’ll become a cartilage cell too,” explains Martin.
Into the clinic
The first patients likely to benefit from this research will be those with traumatic damage to the larynx, and people with rare tracheal disorders. It could also help build tracheas for children who are born with a tightening in their airways - a condition called subglottic stenosis - which causes breathing difficulties.
Alongside this groundbreaking research, the team are compiling the documentation needed to get the green light from the UK regulatory authorities to start clinical trials. Providing enough experimental evidence of the safety and efficacy of a new product is costly, so Martin says that the MRC’s translational funding is “absolutely critical”.
“It’s extraordinarily expensive to make that leap across this great chasm between the laboratory and the first clinical trials - without this level of funding we simply wouldn’t be able to do it,” he says. “So with the help of the MRC, we will have accumulated all of this data by the end of 2012 and be ready to take it into patients next year.”
The benefits of the funding are two-fold because they could also help to get other products off the ground, as Martin explains: “The study we’re working on now is focused on partially rebuilding the larynx. But the data that comes out of it will be applicable to three main products – partial replacement of larynx, complete replacement of adult trachea and complete replacement of paediatric trachea as well. So we’re hoping that this MRC money will pump-prime not just one clinical trial but three simultaneously.”
Building the next generation
Key to realising the benefits of investment in regenerative medicine research in the coming decades will be building up a cohort of skilled surgeons, clinicians and scientists who are able to apply the research to helping patients.
Martin says: “If you don’t have the right people doing the work, with the right aims, skills and motivations, you won’t get anywhere. Here in the UK we’re incredibly blessed with all of those things and the MRC’s at the forefront of supporting these young people going through.”
In July 2012, Martin was part of a team which carried out the first stem cell engineered tracheal transplant on a 13-year-old boy with tracheal stenosis.
Listen to an interview with Martin about progress with the trial in 2014.