Tracheal Transplant Brings High Hopes for Tissue Engineering

When a 30-year-old woman from Colombia who had had severe stenosis from airway tuberculosis was referred to the University College London Centre for Stem Cells and Regenerative Medicine, there were more questions than answers.

The woman was declining in both function and in clinical evaluations. Her airway could not handle stents. The only traditional approach that would have had any chance of curing her, doctors thought, was to remove her entire lung and a major airway.

Then she spoke with Paolo Macchiarini, MD, PhD, Professor of Thoracic Surgery in Barcelona, about the possibility of having a trachea transplant-not just any transplantation, but one in which the specimen she would be given had been mixed with new cells derived from her own stem cells in a bioreactor-an incubator for cells.

Such a procedure had never been tried in a human being before. But researchers told her, We believe it has potential.

Today, about a year after the transplantation, she has regained her pulmonary function and the new trachea has not been rejected. She’s enjoying a normal life looking after her children, said Martin A. Birchall, MD, Professor of Larygnology at University College London and co-leader of the team, who updated an audience on the case at the annual meeting of the American Broncho-Esophagological Association, conducted as part of the Combined Otolaryngology Spring Meeting.

The case strengthens hopes for using stem cells in this kind of transplantation and for the use of stem cells in general.

The attempt was made out of a great need to try something different, Dr. Birchall said. Stents are variably tolerated, he said. And using the whole prosthetic trachea really hasn’t worked at all.

Early Research

Researchers, part of a European network, had been experimenting with such scaffolds in pigs. We found that you could use scaffolds, either synthetic or decellularized human scaffolds, and you could support the airway in a pig quite reasonably for up to a month, but after that they universally fail, Dr. Birchall said. However, if you start adding in cells to the mix, you get a different situation altogether.

Adding epithelial cells increased the duration. But using both epithelial cells and cartilage cells together made a huge difference.

This gives almost indefinite survival in our pig model, he said.

The cartilage cells were grown using the patient’s own stem cells, capitalizing on a discovery at Bristol University of how to ensure that they turn into chondrocytes and not into bone-like cells that cause calcification.