The donated trachea was stripped of the donor’s old cells, down to the inert collagen. The child recipient’s bone marrow stem cells were collected, and applied to the graft in situ in the body, to rebuild the cellular component of the trachea. Thus the child’s own cells will be used to make the new airway sealed and effective.
This is the first time that this has been performed in a child. It is also the first time the entire length of the trachea has been transplanted.
The application of this technology should reduce greatly the risk of rejection of the new trachea, as the child’s stem cells will not generate any immune response.
Background to case
This revolutionary procedure involved close working from a Europe wide team. Lab based scientists and hospital based clinicians worked together to deliver this extraordinary treatment.
A child with Long Segment Tracheal Stenosis has a tiny windpipe that will not grow. It is like breathing through a straw and is a life threatening condition. Working with European partners, Great Ormond Street has developed both a trachea widening operation and a ‘conventional’ transplant programme, as part of a multi-disciplinary team. Around ten UK patients and two European patients receive surgery here a year, with average recovery time now being five weeks.
This boy had had a repair of long segment congenital tracheal stenosis shortly after birth, and later required the then relatively new conventional homograft trachea transplant, now several years ago, The child deteriorated last November when a metal stent used in his trachea began to erode into the aorta, a key artery, causing severe bleeding. A new solution had to be arranged as the risk to the child was severe.
Any transplant from another donor involves rejection risk as the host’s immune system may turn against the donor organ.
Professor Paolo Macchiarini, Careggi University Hospital Florence, Honorary Consultant at GOSH and Honorary Prof at UCL, along with Prof Bader, Director of Stem Cell Biology and Cell Technology, from the University of Leipzig Germany, developed the idea to use the child’s own body as ‘bioreactor’ and the stem cells to regenerate the implanted trachea. Working with the Italian National Transplant Centre, he delivered the de-celled trachea in time.
Surgery at Great Ormond Street was led by Professor Martin Elliott, who developed Europe’s first specialist tracheal surgery service for children, and who had carried out the previous tracheal transplant on this child. Before replacing the trachea, complex cardiac surgery was necessary to repair the aorta
Dr Mark Lowdell and colleagues (Maryam Sekhavat and Edward Samuel) at The Royal Free Hospital, UCL Medical School, received the donor trachea from Italy and some bone marrow from the patient at the beginning of surgery. The team prepared two different types of stem cells from the patient’s own bone marrow together with some growth signalling chemicals and returned them to GOSH with the donor trachea for the surgery.
Prof Macchiarini applied the cells and the growth factors to the trachea in the operating theatre so that the cells that would grow inside the tissue to allow the trachea to becoming a working organ. Professor Macchiarini calls this a ‘bionic’ process, using specific cytokine drugs to make the stem cells differentiate and rebuild the trachea.
The fourth key co-worker was Professor Martin Birchall, UCL Lead for translational regenerative medicine. Also a UCL Ear Hospital consultant surgeon specialising in airways and voice. Among other roles, Professor Birchall and Dr Lowdell obtained UK ethics and regulatory approval.
Clarification on cases
Professor Macchiarini, Professor Birchall and colleagues in the UK, Italy and Spain successfully carried out the world’s first stem cell based airway transplant in young woman in 2008, who remains well to this day. However this involved the cells being developed outside the body.
The new technique – where the cells develop inside the body – is considerably simpler and potentially applicable to many centres around the world, including those in poorer countries.
This patient is the first child, and the second patient, to have this technique.