News Release

First operation for transplantation of a tissue-engineered airway is successful

Gives huge increase in quality of life for recipient

Peer-Reviewed Publication

The Lancet_DELETED

The first operation for transplantation of a tissue-engineered airway has been successful, and has massively improved the quality of life of the 30-year-old Colombian female recipient,* a mother of two, who needed the transplant after contracting tuberculosis. These pioneering results are reported in an Article published Online first and in an upcoming edition of The Lancet. The work was done by a team from four institutions: Hospital Clínic of Barcelona (Universitat de Barcelona), Spain, University of Bristol, UK, Politecnico di Milano, Italy, and University of Padua, Italy, and was led by Professor Paolo Macchiarini (Hospital Clínic of Barcelona).†

The loss of a normal airway is devastating, and attempts to replace large airways have met with serious problems, such as graft necrosis, lethal bleeding, and severe and life-threatening infections. Pre-requisites for a tissue-engineered replacement are a suitable matrix, cells, ideal mechanical properties, and the absence of antigenicity (rejection). The team removed the cells from a human donor trachea, principally because these cells have transplant rejection antigens. The decellularised trachea was then readily colonised with cartilage cells (chondrocytes) derived from the patient's own stem cells, and epithelial cells taken from a healthy part of her trachea. This graft was then used to replace the recipient's left main bronchus—which connects the main windpipe (trachea) to the left lung. Her own left bronchus had been damaged by an irreversible, end-stage collapse (malacia).

The recipient had no complications from the operation and was discharged from hospital on the 10th postoperative day. She has remained well since, and is able to walk up two flights of stairs, walk 500 m without stopping, and, perhaps most importantly, care for her children. The graft had a normal appearance and properties at 4 months, and the patient had no anti-donor antibodies and did not need to take immunosuppressive drugs. The graft also developed its own blood supply, with active bleeding within 30 days.

The authors conclude: "The results show that a cellular, tissue-engineered airway can be produced with mechanical properties that allow normal functioning, and which is free from the risks of rejection. This patient provides new evidence that autologous‡ cells combined with appropriate biomaterials might provide, in future, successful functional solutions for serious clinical disorders."

They add:§ "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. We hope that these future patients will no longer suffer the trauma of speech loss, severe shortness of breath and other limited clinical and social activities."

Claudia Castillo adds¶: "The possibility of avoiding the removal of my entire lung—and, instead, replacing only my diseased bronchus with this tissue engineering process—represented a unique chance for me to return to a normal life that I am now enjoying with my children and family. I was scared at the beginning because I was the first patient but had confidence and trusted the doctors. I am now enjoying life and am very happy that my illness has been cured."

In an accompanying Comment, Dr Toshihiko Sato and Dr Tatsuo Nakamura, Institute for Medical Sciences, Kyoto University, Japan, say the achievements of Macchiarini and colleagues in these difficult settings should be highly regarded. They conclude: "However, to better evaluate the results of their findings, we look forward to follow-ups from longer observation periods."

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For Professor Paolo Macchiarini, Hospital Clínic of Barcelona, please contact Marc de Semir or Àlex Argemí, Corporative Communication Direction of the Hospital Clínic of Barcelona. T) +34932275700/ +34 627947528

For Professor Martin Birchall and Professor Anthony Hollander, University of Bristol, please contact Cherry Lewis, Press Office. T) +44 (0) 117 928 8086 07729 421 885

Dr Sara Mantero, Politecnico di Milano, Italy. T) +39 02 23993376
For Dr Maria Teresa Conconi, University of Padua, Italy, contact should be made via Professor Paolo Macchiarini as above.

Comment Dr Toshihiko Sato, Institute for Medical Sciences, Kyoto University, Japan. T) +81 75 751 4149

Notes to editors:

*A full biography of the patient, Claudia Lorena Castillo Sánchez, is available in the additional materials supplied with this release (see below). Her children are Johan (15 years old) and Isabella (4 years old).

†Please see appendix in e-mail for full details of which part of the team did what, and also other links for photo and video footage.

‡Autologous=cells from the recipient.

§quote direct from author and cannot be found in text of Article.

¶quote direct from Claudia Castillo and cannot be found in text of Article.

Links to extra material:

For full Lancet Article and Comment: http://press.thelancet.com/airwaypapersfinal.pdf

For Hospital Clínic of Barcelona press release: http://press.thelancet.com/AIRWAYBARCELONARELEASE.doc

For University of Bristol, UK, press release: http://press.thelancet.com/AIRWAYBRISTOL.doc

For PowerPoint presentation used by the authors at the press conference (minus complex graphics) : http://press.thelancet.com/AIRWAYPRESENTATION.ppt

For a profile of Claudia Lorena Castillo Sánchez: http://press.thelancet.com/AIRWAYCLAUDIAPROFILE.pdf

For video footage and photos of Claudia; plus full translations and interview with Dr Paolo Macchiarini; and full PowerPoint presentation complete with graphics please visit Hospital Clínic of Barcelona server at: ftp://lancet:clinic@ftp.clinic.ub.es

Jpegs of Claudia: http://press.thelancet.com/claudiacastillo1.JPG
http://press.thelancet.com/claudiacastillo2.JPG
http://press.thelancet.com/claudiacastillo3.JPG


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