First trachea transplant without immunosuppression

• Tissue engineering has made possible this doubly innovative operation - the first trachea transplant and the first tissue transplant to be performed without the need for immunosuppression.
• Professor Paolo Macchiarini, Head of the thoracic surgery department of Hospital Clínic has led the basic research and the international team formed by the universities of Bristol, Padua and Milan, who contributed to this success.
• The transplanted tissue is a hybrid from a donor that was repopulated with stem and epithelial cells from the recipient. Five months later, Claudia Castillo, who required the operation to save a lung following tuberculosis, is in perfect health.

Barcelona, Tuesday, 18 November 2008: After 4 years of going from consultation to consultation, Claudia Castillo finally found a solution to her respiratory problems. The young Colombian woman suffered from a cough that took a long time to be diagnosed as tuberculosis. She arrived at Hospital Clínic of Barcelona with complications and there, she met Professor Paolo Macchiarini Head of the Thoracic Surgery Department, who had led the international team that made possible the first trachea transplant and the first tissue transplant without immunosuppression. She underwent an operation on the upper part of the trachea but nothing could be done to repair the blockage in the left lung. The infection had led to a severe collapse just before the branch of the trachea and this obstruction prevented air from reaching the lung. The only treatment option at the time involved removing the affected lung. As the young mother of two children, removing the lung would have considerably reduced quality of life for Claudia Castillo. In March 2008, her situation worsened to the point where she was unable to carry out domestic chores or look after her children, so intervention became urgent. In June, after obtaining authorization from the ethics committee of Hospital Clínic of Barcelona and from the Catalan Transplant Organization (OCATT), the first trachea transplant and the first tissue transplant of any kind without immunosuppression took place.

The study, which will be published online on Wednesday by the journal The Lancet, with Professor Paolo Macchiarini as the principal author, together with his colleagues Dr. Philip Jungebluth, Dr. Tetsuhiko Go and Dr. Jaume Martorell, presents the details of this transplant - the first treatment alternative for treating the collapsed trachea that the patient was suffering from. The technique consists of depleting the trachea to be transplanted of the donor's cells and repopulating it with cells from the recipient before the operation. Thus, thanks to tissue bioengineering, the donor trachea becomes a hybrid that the recipient's body identifies as its own, thereby making immunosuppression unnecessary. The transplant and most of the processes involved were carried out at Hospital Clínic of Barcelona, but this would have been impossible without the collaboration of the University of Bristol (UK), the University of Padua (Italy) and the University of Milan (Italy). The prior basic research was led by Professor Paolo Macchiarini.

The process of preparing the trachea requires many cycles of washing to eliminate all the donor cells - many more than those suggested by the basic research. The tissue was a 7-cm segment of trachea from a 51-year-old donor who had died from brain hemorrhage. The team of Dr. Maria T. Conconi at the University of Padua (Italy) confirmed that, after 25 washing cycles, the trachea treated at Hospital Clínic was free from donor antigens - the molecules that would cause the tissue to be rejected by the recipient. Meanwhile, at the University of Bristol, the teams of Professor Martin Birchall and Professor Anthony Hollander cultivated the recipient's cells that would later be introduced into the trachea. These cells were epithelial cells taken from the trachea and cartilage cells (chondrocytes), differentiated from stem cells taken from the patient's bone marrow. This technique was initially designed to treat cases of osteoarthritis. Back at Hospital Clínic, the team of Professor Paolo Macchiarini introduced these cells into the trachea using a bioreactor designed by the team of Dr. Sandra Mantero at the University of Milan. The epithelial cells were inserted into the inner surface of the trachea and the chondrocytes covered the outer surface. The donor tissue thus became a hybrid very similar to new tissue from the patient themselves.

The operation was performed 4 days later at Hospital Clínic, where the thoracic surgery team extracted the damaged section of trachea and replaced it with the new trachea. This pioneering operation was not without question marks but if anything had gone wrong, it would have been changed to a lung-resection operation - the classical treatment choice. Thanks to the skill of the surgeons and the huge international effort, the operation was a success. Five months later, the lung that had been so long out of use was providing normal respiration.

This innovation in biomedicine and surgery may become an alternative for diseases of the upper airways, such as congenital deformities or primary tumors, which cannot currently be treated using conventional surgical techniques. The clinical application of stem-cell cultures and the prevention of the problems deriving from immunosuppression are a milestone in the history of transplantation. There are already some cases being studied that may benefit from the new technique and research continues into improving the process. If all goes well, Claudia Castillo will be just the first patient to benefit from a new advance led by researchers from Hospital Clínic of Barcelona.

Source : IDIBAPS - Institut d'Investigacions Biomèdiques August Pi i Sunyer