Stem-cell science moves forward

In the hierarchy of transplant surgery, replacing a bronchus (the passage from the main windpipe, the trachea, into a lung) does not sound difficult compared with, say, plumbing in a new heart. In fact, until a few months ago, it had never been attempted.

The reason was not that the surgery itself would be hard but that the tissue in question, which is the first line of defense against the bacteria and viruses that come with every lungful of air, has a remarkably active immune response. So active, indeed, that if you transferred part of an airway from one person to another, the resulting immunological conflict would probably kill the recipient. Because a weak bronchus, though debilitating, is seldom life-threatening, transplant surgeons have left well enough alone.

In a blaze of publicity in late November, that changed. A paper in the Lancet, published by a team led by Dr. Paolo Macchiarini of the Hospital Clinic in Barcelona, Spain, described such an operation, carried out in June on a patient named Claudia Castillo, whose left bronchus had been damaged by tuberculosis. The reason for the publicity, though, was not that this was the first bronchial transplant but that it involved some serious bioengineering using stem cells.

Stem cells exist to replenish the supply of other cells. When a stem cell divides, it sometimes produces daughters that are different from one another. One is another stem cell. The other is the first step on the path to a particular sort of tissue such as the lining of a windpipe. The idea behind stem-cell bioengineering is to use the recipient's own stem cells to create an artificial organ that will be recognized as part of the body by the recipient's immune system, and thus not rejected. And this, in the case of Castillo's new bronchus, is what Macchiarini and his team have done.

To make an artificial organ requires two things. One is the right sort of cells. The other is a framework on which to grow those cells so that they take the right shape. Previous projects of this sort, which have successfully created artificial skin and artificial bladders, have relied on synthetic frameworks. A windpipe, though, is a more complicated structure than skin or a bladder. The starting point for Castillo's transplant, therefore, was a piece of trachea removed from a dead donor.

The team stripped this of its cells (and thus of the antigens that provoke an immune response) by treating it with a special detergent. That left a trachea-shaped piece of cartilage. They then took samples of Castillo's other bronchus and also her bone marrow and grew them as cell cultures. The bronchial samples consisted mainly of what are known as epithelial cells, and with these it was just a question of multiplying their numbers. The bone marrow was the source of the stem cells that made the procedure newsworthy.

Most bone-marrow stem cells generate blood cells. A few, though, can produce chondrocytes, the cells that make cartilage. The team extracted these, cultured them and then used a special growth factor to persuade them to spin off chondrocytes.

Epithelial cells and chondrocytes were applied liberally to the treated trachea, and the result, when it had settled down into something that resembled a natural windpipe, was transplanted into Castillo. She has now made a full recovery.