World's first windpipe transplant and regeneration in a child

19 March 2010

British and Italian doctors have achieved a world first in transplanting a donated "stripped down" trachea into a boy and using his own stem cells to rebuild the cellular structure in his body.

The boy had life-threatening condition affecting his trachea — long segment tracheal stenosis — which resluts in a tiny windpipe that will not grow. He also had serious damage to his aorta caused by a metal stent previously implanted to repair the trachea.

The operation was carried out at the Great Ormond Street Hospital (GOSH) in London last Monday. In preparing for the operation, the donated trachea was stripped of the donor’s old cells, down to the inert collagen. The boy's bone marrow stem cells were collected and applied to the graft 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 revolutionary procedure involved close working from a Europe-ide team. Lab-based scientists and hospital-based clinicians worked together to deliver this extraordinary treatment.

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 prepared the de-celled trachea for the operation.

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.

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 use of the boy's own stem cells to rebuild the cellular structure will not generate any immune response.

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.

Related information

First successful transplantation of a synthetic windpipe seeded with patient's own stem cells. 8 July 2011