Sunday, November 23, 2008

Europeans Announce Pioneering Surgery

PARIS — Physicians at four European universities have successfully transplanted a human windpipe, using stem cells from the recipient’s own bone marrow to reline a donor trachea and prevent its rejection by her immune system, according to an article in the British medical journal The Lancet.

The operation, performed in June, was the first to use stem cells in transplanting an airway, and is considered an important advance because it allowed the surgeons to replace a larger segment than had generally been possible in the past. The hope is that the stem cells will transform themselves into the kind of cells that normally line the windpipe and carry out important functions such as clearing mucus out of the airway.

Similar techniques using other types of cells from patients have been used to fashion bladders and also to grow skin for grafting.

In this case, surgeons used stem cells from the patient’s bone marrow because they have the ability to transform themselves into different types of tissue. In that sense, the marrow cells are similar to embryonic stem cells, but they are free of the ethical issues raised by the use of embryonic cells. It is not certain whether the transplanted stem cells have continued to function in the patient or whether other cells from her body have become part of the new airway.

A surgeon not associated with the case, Dr. Eric M. Genden, chairman of otolaryngology at Mount Sinai Hospital in Manhattan, said the report seemed promising, but added: “I would take the results cautiously. Time will tell.”

Dr. Genden predicted that the work would not turn out to be a panacea for people with diseased or damaged tracheas, or windpipes. He said that other teams had tried partial tracheal transplants, with mixed success, and that he had done a dozen from 2005 to 2007, using the patients’ own skin cells, not stem cells, to line the trachea. All are still in place, but so far it has not been possible to replace an entire trachea, he said.

“I have one of the largest populations of patients with these problems in the U.S., and unfortunately, they’re all going to be calling about this,” Dr. Genden said.

The transplant operation described in The Lancet was performed on a 30-year-old woman, Claudia Castillo, in June in Barcelona to relieve severe shortness of breath and damage to her airway caused by tuberculosis. The surgery followed weeks of preparation carried out at the universities of Barcelona, Spain; Bristol, England; and Padua and Milan in Italy.

Ms. Castillo was hospitalized in March because her left bronchus — the tube connecting the windpipe to the left lung — was so badly damaged by tuberculosis that she was unable to walk more than a few steps at a time, according to a statement from Bristol University.

“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 Prof. Paolo Macchiarini of the University of Barcelona, who performed the operation. “Just four days after transplantation the graft was almost indistinguishable from adjacent normal bronchi.”

Moreover, 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 Bristol University statement said.

Martin Birchall, a professor at the university, said the transplant showed “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.”

The Bristol University statement said a segment of trachea, roughly three inches long, was taken from a 51-year-old donor who had died of a cerebral hemorrhage. Using a new technique developed in Padua University, the trachea was stripped of its donor’s cells over a six-week period “so that no donor cells remained,” the statement said.

At the same time, at Bristol University, stem cells removed from Ms. Castillo’s bone marrow, and cells taken from one of her lungs, were grown into “a large population” and used to “seed” the donated windpipe using a new technique developed in Milan to incubate cells. Her cells embedded themselves in the cartilage of the donor’s trachea.

Four days after the seeding, the graft was used to replace Ms. Castillo’s damaged bronchus.

Normally after transplants there is a high risk of rejection because the recipient’s immune system attacks the foreign organ. Most transplant patients, thus, need immunosuppressant drugs to prevent rejection.

“The patient has not developed antibodies to her graft, despite not taking any immunosuppressive drugs,” the statement from Bristol University said.

Alan Cowell reported from Paris, and Denise Grady from New York.


By ALAN COWELL and DENISE GRADY

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