Consider a kiss. The bestower must be able to breathe while pursing his or her lips, so “if there’s no air flow through your mouth or nose, you can’t give somebody a smooch,” said Peter Belafsky, MD, PhD, principal investigator of the laryngeal transplant project at the University of California, Davis, Medical School.
Explore This IssueApril 2013
In other words, one of the most iconic ways for humans to connect with each other requires a functioning larynx. Intrepid clinicians and researchers are using regenerative medicine techniques to help people whose ability to speak, sing, hear—or yes, kiss—has been impaired.
In Europe, an international team of surgeons and scientists has been transplanting stem cell-based tracheas since 2008. “We stripped the cells off the donor trachea, leaving just the extracellular matrix as a scaffold,” said Martin Birchall, MD, professor of laryngology at University College London Ear Institute. “Then we seeded the scaffold with stem cells taken from the patients’ own bone marrow.” The scaffold was bathed in a cocktail of hormones and growth factors to coax the growth of cell types associated with a normal trachea. In 2010, Dr. Birchall and colleagues, including pediatric cardiothoracic surgeon Martin Elliott, MD, performed the first pediatric, stem cell-based, tissue-engineered transplant, on a 10-year-old boy with congenital tracheal stenosis and pulmonary sling. He urgently needed a new trachea because the metal stent placed soon after his birth had eroded into his aorta, causing it to bleed. The patient, now 13, has a functioning airway.
But in early 2011, the team treated a 36-year-old man with a rapidly growing laryngeal tumor. This patient didn’t have the luxury of waiting for a donor trachea. Instead, bioengineers at the University College London developed an artificial laryngotracheal scaffold from plastic. Then, just as with a cadaver trachea, it was seeded with stem cells and incubated in the growth medium, and within two days, the patient had his new airway. A few months later, a 30-year-old man, also with an inoperable tracheal tumor, underwent a similar operation. These two patients became the first humans to receive stem cell-based organ transplants. So far, the original patient is doing well, but the second patient has died, for reasons seemingly unrelated to the implant. In the meantime, two more patients, both from Russia, have received engineered tracheas.
“There is a huge need to replace conventional organ donation, due to the infection risk and the risks associated with immunosuppression,” said Dr. Birchall. “We’d like to continue refining these techniques into good manufacturing processes. They are now quicker, cleaner and safer than ever before, and are ready for testing in clinical trials.”