Synthetic Windpipe Is Used to Replace Cancerous One

Surgeons in Sweden have replaced the cancerous windpipe of a Maryland man with one made in a laboratory and seeded with the man’s cells.

Thomas Grosse/Harvard Bioscience

A trachea made from plastic, above, and seeded with stem cells was successfully implanted in a Baltimore man in Sweden.

The windpipe, or trachea, made from minuscule plastic fibers and covered in stem cells taken from the man’s bone marrow, was implanted in November. The patient, Christopher Lyles, 30, whose tracheal cancer had progressed to the point where it was considered inoperable, arrived home in Baltimore on Wednesday. It was the second procedure of its kind and the first for an American.

“I’m feeling good,” Mr. Lyles said in a telephone interview from his home, where he was playing with his 4-year-old daughter. “I’m just thankful for a second chance at life.” He said he hoped to resume his job, as an electrical engineer with the Department of Defense, as soon as he regained full strength.

“He went home in very good shape,” said Dr. Paolo Macchiarini, director of the Advanced Center for Translational Regenerative Medicine at the Karolinska Institute in Stockholm.

Dr. Macchiarini is a leader in the field of tissue engineering, in which the goal is to produce replacement tissues and organs outside the body. Research in the field has undergone a resurgence in recent years because of advances in understanding stem cells — undifferentiated cells that can proliferate and be induced to become cells of a specific type of tissue.

“What we did is surgically remove his malignant tumor,” Dr. Macchiarini said. “Then we replaced the trachea with this tissue-engineered scaffold.” The Y-shaped scaffold, fashioned from nano-size fibers of a type of plastic called PET that is commonly used in soda bottles, was seeded with stem cells from Mr. Lyles’s bone marrow. It was then placed in a bioreactor — a shoebox-size container holding the stem cells in solution — and rotated like a rotisserie chicken to allow the cells to soak in.

After two days, it was installed in Mr. Lyles during an elaborate operation in which it was sutured to his throat and lungs. All told, the treatment cost about $450,000, Mr. Lyles said.

David Green, the president of Harvard Bioscience, the Massachusetts company that made the bioreactor, said that once the cells were inside the scaffold, they began to grow and divide and produce cartilage. “After two or three days, I think you can realistically call it tissue,” he said.

While special compounds called transcription factors were used to help force the stem cells to differentiate into trachea-specific cells, Dr. Macchiarini said that once the windpipe was implanted the cells continued to grow and differentiate, presumably because of chemical signals produced by the body. “We’re using the human body as a bioreactor to promote regeneration,” he said.

Because Mr. Lyles’s own cells were used, there is no need for drugs to prevent his body from rejecting the windpipe, which is a common problem in transplants using donated organs.

But Alan O. Trounson, the president of the California Institute for Regenerative Medicine, said that although rejection would not be a problem, the body responds to any foreign object, often by trying to encapsulate it. While he described Dr. Macchiarini’s work as “terrific,” he said he was not sure how long such a transplant could be expected to last.

“It looks very functional at this stage,” Dr. Trounson said. “But there’s going to be a reaction of some kind.” More work will probably be needed to develop scaffold materials that are optimized to reduce the response, he added.

Dr. Macchiarini has performed a dozen trachea transplants since 2008, but the first 10 used organs from cadavers in which all the living cells were removed, leaving behind a natural scaffold of cartilage. Donated tracheas are rare, however, and are never a perfect fit. In Mr. Lyle’s case, and in the case of an Eritrean man who received a similar transplant last June and is doing well, the synthetic scaffold is made using CT scans of the existing trachea to ensure it matches precisely.

The field of tissue engineering has gone through periods of boom and bust, as predictions that companies would one day be fabricating hearts and other complex organs have not come close to fruition. But there have been successes with simpler tissues like skin — a few products are on the market — and with another organ, the bladder, which, like the trachea, is relatively simple. Researchers at Wake Forest University have successfully built tissue-engineered bladders and transplanted them into patients with spina bifida.

http://www.nytimes.com/2012/01/13/health/research/surgeons-transpla...

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