1 April 2009
Claudio Castillo's life was transformed by pioneering bone marrow stem cell work.
Although the stem cell techniques developed by Professor Anthony Hollander of the Department of Cellular and Molecular Medicine and commercialised by Azellon are not exactly those that transformed Claudia’s life, the bone marrow stem cells used in cell bandages are the same as those used to treat her.
One Sunday lunchtime in March, Anthony Hollander received a call from his colleague Martin Birchall, Professor of Thoracic Surgery: “I was having a pub lunch with my family when Martin rang me about this woman who needed a new windpipe,” says Hollander. “My first reaction was that it was crazy to think we could put together a plan to save her in just a few weeks. My second was that it was a chance to prove that what we had been saying for so long was actually true – that you can use tissue engineering and adult stem cells to make a difference to patients’ lives.”
Claudia Castillo, a young Colombian mother of two now living in Barcelona, had spent years in and out of hospital after a rare form of tuberculosis blocked her airways, making breathing increasingly difficult. Professor Paulo Macchiarini, Head of Respiratory Surgery at the Hospital Clinic de Barcelona, who has collaborated with Birchall for many years, offered her the possibility of a cure with a procedure never before carried out on humans. In a pan-European effort, the team set about creating the first tissue-engineered trachea, using the patient’s own stem cells.
Building on successful laboratory work previously performed by the team, it was proposed that the lower trachea and the tube to the patient’s left lung (bronchus) should be replaced with the bioengineered airway, based on the scaffold of a human trachea. A seven-centimetre tracheal segment was donated by a 51-year-old transplant donor who had died of cerebral haemorrhage – Spain has a policy of presumed consent for organ donation. Using a new technique developed in Padua University, the trachea was decellularised over a six-week period so that no donor cells remained.
Adult stem cells were obtained from Claudia’s own bone marrow, grown into a large population and matured into cartilage cells (chondrocytes) in Birchall’s lab in the Department of Clinical Veterinary Science, using an adaptation of the method devised by Hollander for treating osteoarthritis. The donor trachea was then seeded with chondrocytes on the outside, using a novel bioreactor that incubates cells, developed at the Politecnico di Milano, Italy, allowing them to migrate into the tissue under conditions ideal for each individual cell type. In order to replicate the lining of the trachea, epithelial cells were seeded on to the inside of the trachea using the same bioreactor.
Four days after seeding, the graft was used to replace the patient’s left main bronchus. The operation was performed by Macchiarini on 12 June 2008, at the Hospital Clinic de Barcelona. Just four days after transplantation, the graft was almost indistinguishable from adjacent normal bronchi and ten days after the operation Claudia was discharged from hospital. After one month, a biopsy elicited local bleeding, indicating that the blood vessels had already grown back successfully.
The alternative for Claudia was to remove her left lung, which would have left her impaired for life. However, making the decision to be the first person ever to have such a new and radical operation was a tough choice. “It really is a miracle,” she says. “The problem has gone. I made the right decision. I can go to the park and I can play with my children. I hope to start back at my job as a dental nurse in the New Year. I now have a future to look forward to.” The science behind her operation marks a new era in medicine.