A 30-year old Columbian woman living in Spain whose airway was damaged from tuberculosis is the first person in the world to receive a new airway engineered from tissue that was grown from her own stem cells which means she is likely to have a much better quality of life because she will probably not have to take drugs for the rest of her life to stop her immune system rejecting the tissue.

The operation is described in a paper published in the early online issue of the The Lancet on 19 November. Specialists from four European institutions came together to carry out the operation: the Hospital Clínic of Barcelona, part of Universitat de Barcelona in Spain, the University of Bristol in the UK, the Politecnico di Milano in Italy, and the University of Padua, also in Italy. Professor Paolo Macchiarini of the Hospital Clínic of Barcelona led the procedure.

As well as producing a good outcome for the patient, Claudia Castillo, who said thanks to this operation she has the opportunity to "return to a normal life", the significance of this innovative procedure is that it shows it is possible to create a cell-based, tissue-engineered airway that not only works properly but is also free of the risk of rejection, opening the way for treating other serious diseases by using biomaterials combined with tissue cultured from patients' own stem cells.

Castillo said in a press statement that she was scared at first because she would be the first person in the world to receive such a treatment, but she said she trusted her doctors and had confidence in them. The alternative to replacing her diseased bronchus with the new tissue engineered airway would have been complete removal of her lung. Castillo said she had the unique chance to return to a normal life with her two young children and family.

"I am now enjoying life and am very happy that my illness has been cured," she said.

Traditional attempts to replace damaged airways often meet with serious problems such as life-threatening infections, lethal bleeding and dying off (necrosis) of the grafted tissue.

In this case the doctors used the trachea of a human donor and removed the donor's cells in order to get rid of the antigens that the recipient's immune system might react to and reject. This left just a decellularized "scaffolding" which was colonized with two types of cell from the recipient: cartilage cells (chondrocytes) and epithelial cells. The cartilage cells were grown from the recipient's own stem cells and the epithelial cells were taken from a healthy part of her trachea.

The doctors then performed an operation that took out the damaged section of the patient's airway - the left main bronchus that joins the windpipe to the left lung (this had collapsed irreversibly, known as malacia) - and replaced it with the new tissue engineered graft.

Castillo had no post-operative complications and was discharged ten days later. Four months later her graft appears normal and has grown its own blood supply, her body has not produced anti-donor antibodies, and she is not taking drugs to suppress her immune system.

Her health is described as good: she can walk 500 m (nearly a third of a mile) without stopping, she can climb two flights of stairs, and care for her children.

The authors concluded that:

"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."

"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," they added.

Drs Toshihiko Sato and Tatsuo Nakamura, from the Institute for Medical Sciences at Kyoto University in Japan wrote in an accompanying comment that this achievement in such difficult circumstances should be highly regarded, but they cautioned that more follow up over longer periods of observation were still needed to "better evaluate the results" of the findings.

"Clinical transplantation of a tissue-engineered airway."
Paolo Macchiarini, Philipp Jungebluth, Tetsuhiko Go, M Adelaide Asnaghi, Louisa E Rees, Tristan A Cogan, Amanda Dodson, Jaume Martorell, Silvia Bellini, Pier Paolo Parnigotto, Sally C Dickinson, Anthony P Hollander, Sara Mantero, Maria Teresa Conconi, Martin A Birchall.
The Lancet, Early Online Publication, 19 November 2008

Click here for Abstract.

Sources: The Lancet.

: Catharine Paddock, PhD

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