Stem Cell-Based Organ Transplants Emerging as Alternative to Conventional Donations

Building a Better Larynx

The trachea is an attractive candidate for bioengineering, said head-and-neck surgeon Marshall Strome, MD, who is affiliated with New York’s Head and Neck Surgical Group and a group of collaborative airway specialists at Roosevelt Hospital that is studying tracheal transplantation. “Decellularized airway scaffolds, together with autologous or allogeneic hypo-immunologic stem cells, can be transplanted without the need for immunosuppression,” he said. He believes that synthetic tracheas hold great potential, but wondered, “What happens to those transplants over the long term?” He also pointed out that it is one thing to fashion a few inches of trachea but another to build a whole organ. “However, with increased understanding, we should be able to integrate genetically directed cellular products, and then, who knows?”

Still, the trachea is an easier target than the larynx, which Dr. Belafsky considers to be the most complex neuromuscular organ in the body. “We’re not there yet for a total laryngeal transplant, because you need sensation, among other things,” said Dr. Strome, who performed the first U.S. laryngeal transplant more than 14 years ago. Some investigators have proposed partial transplants using scaffolds made of cartilage and seeded with stem cells in much the same way as the tracheal implants were created. “This will permit the replacement of larger segments of the larynx than was previously thought possible, without the need for lifelong immunosuppression. But it will still require a functioning neuromuscular-cartilage complex, so you would have to leave the arytenoid cartilages behind.” Similarly, a tissue-engineered larynx currently would be suitable only for partial transplants, because “we need that functional myoneural-cartilage unit.”

Two years ago, surgeons at the University of California, Davis, led by D. Gregory Farwell, MD, performed the world’s second reported laryngeal transplant, on a patient of Dr. Belafsky. The larynx is unique, and uniquely difficult, for several reasons, Dr. Farwell said. First, unlike most transplanted organs, which perform single functions, the larynx has multiple complex jobs, providing not just an airway but also a vehicle for the voice and protection for safe swallowing. Also, unlike a liver transplant, a laryngeal transplant is not a life-saving surgery, although it can have a profound impact on the patient’s quality of life. “This intensifies the ethical considerations, with more attention given to specific risks and benefits,” he said. The surgery two years ago went well, but it was “humbling how challenging this was for us as surgeons,” Dr. Farwell added. Perhaps the most important lesson he learned was that “Dr. Strome’s initial laryngeal transplant success is reproducible. That has huge implications for the field.”