A Giant Leap Forward in Stem Cell Transplantation

Topiary is the art of creating sculptures in the medium of clipped trees and shrubs. However, in modern topiary, shaped wire cages are often covered by small-leaved ivy to give the look of topiary in a shorter amount of time. This same premise is now being used in medicine. You may recall a concept study we told you about just days ago where cardiologists harvested stem cells from umbilical cord blood collected at birth and seeded them onto eight biodegradable scaffolds. Over time, the scaffolds will dissolve, leaving behind fully formed heart valves, which could one day be used to replace those of children born with heart valve defects. Not only would the heart valve grow as the child develops, but using the child’s own stem cells would eliminate the need for anti-rejection drugs. Now, in another groundbreaking development, doctors in Europe have grown and successfully transplanted the first trachea made from a segment of a donated trachea (the scaffold) and a young woman’s own stem cells. 

The procedure was an extraordinary collaboration of physicians at four European universities in Barcelona, Spain; Bristol, England; and Padua and Milan in Italy. According to the Bristol University statement, the roughly three-inch long segment of trachea was stripped of its donor’s cells using a new technique developed in Padua University, a process that took six weeks. During the same time, at Bristol University, stem cells removed from the woman’s bone marrow, along with cells taken from one of her lungs, were grown into “a large population.” Once removed from their culture media, there was then a sixteen-hour window in which the cells had to be transported from the Bristol lab to Barcelona, after which they would have been unusable.

According to the BBC, Easyjet Airlines was slated to transport the cells. Professor Martin Birchall, one of the lead researchers, had conversed with the airline up to hours before the flight, in which he was told it could carry the cells. But when the cells arrived, the “check-in staff said that they couldn’t take the material onboard and that it could have been some kind of dangerous material,” according to Professor Anthony Hollander, one of the scientists involved. Fortunately, Philip Jungerbluth, a German medical student who was due to accompany the cells on the flight, knew a thoracic surgeon from Germany who he said used to fly. “We had a couple of conversations, and within two hours the surgeon was in Bristol—with his private jet,” said Birchall. “If we hadn’t been able to get the cells there, we would have wasted years of work and this major breakthrough for surgery and science wouldn’t have taken place.”

Once the cells arrived in Barcelona, they were used to “seed” the donated trachea using a new technique developed in Milan. The seeded cells embedded themselves in the cartilage of the donated trachea. In June, four days after the seeding, doctors at Hospital Clinic transplanted the graft into 30-year-old Claudia Castillo, who had been hospitalized in March after her left airway collapsed as a result of tuberculosis. Efforts to reopen the airway with a stent were unsuccessful, and the stent was removed. “The only conventional option remaining was a major operation to remove her left lung which carries a risk of complications and a high mortality rate,” the statement said. 

“We are terribly excited by these results,” said University of Barcelona’s Paolo Macchiarini, M.D., who performed the operation. “Just four days after transplantation the graft was almost indistinguishable from adjacent normal bronchi.” Two months after the surgery, lung function tests on Ms. Castillo “were all at the better end of the normal range for a young woman,” the statement said. Four months after the surgery, Ms. Castillo was still doing well. By then, she could “walk up two flights of stairs, walk 500 meters without stopping, and care for her children, aged 4 and 15,” the authors write. And, because the transplant relied on the patient’s own stem cells, there was no need for drugs to prevent rejection. “The patient has not developed antibodies to her graft, despite not taking any immunosuppressive drugs.”

“Surgeons can now start to see and understand the very real potential for adult stem cells and tissue engineering to radically improve their ability to treat patients with serious diseases. We believe this success has proved that we are on the verge of a new age in surgical care,” said Professor Birchall, who oversaw the growing of the stem cells. “In 20 years this will be the most common form of surgery,” he added.

In an editorial published with the trachea transplant report, Toshihiko Sato and Tatsuo Nakamura, of the Institute of Frontier Medical Sciences at Japan’s Kyoto University, said the initial results of the surgery should be “highly regarded,” but that more information and a longer follow-up is needed to fully evaluate the results. Macchiarini’s team agrees that more than six months of follow-up would be helpful before the procedure is tested in a clinical trial. “We think that this first experience represents a milestone in medicine and hope that it will unlock the door for a safe and recipient-tailored transplantation of the airway in adults and children,” the team said.

Special Note: In a statement, Easyjet told the BBC: “We do not have any record of the passengers request to carry medical materials onboard the flight. However, as a gesture of goodwill, Easyjet has refunded the passenger for the cost of his flight.”

The transplant report and accompanying editorial was published in the British medical journal The Lancet.