Let’s blow away all the barriers to stem-cell science

It is an amazing achievement.

A year ago, Claudia Castillo could not walk a flight of stairs without becoming breathless and was unable to work or enjoy playing with her children. Tuberculosis damaged her airway and starved her left lung of oxygen (1). Patients with this problem normally face removal of the starved lung with obvious negative implications for the quality and length of life.

An alternative approach is to repair the airway with a donor transplant, which avoids the need for lung removal as it can now receive oxygen normally. Previously, however, this option was avoided for all but the most desperate cases, because receiving a donor airway meant a lifetime of immunosuppressant drugs to prevent rejection. And a lifetime of immunosuppressant drugs means a lifetime of opportunistic infections that also have obvious negative implications for the quality and length of life.

In the case of Claudia Castillo, however, Professor Paolo Macchiarini of Barcelona and his colleagues in Milan, Italy and Bristol, England have solved this problem of rejection. They took a piece of airway from an organ donor and then stripped off all the donor cells, leaving just a scaffold of collagen. Stem cells were then taken from Castillo’s hip marrow, healthy airway and nose. The stem cells were flown to Bristol where they were grown into cartilage and other cells that were then flown back to Barcelona. The donor scaffold of collagen was then combined with the cartilage and other cells grown from Castillo’s stem cells in a rotating bioreactor.

The piece of airway, the bioengineered trachea graft, was then cut to shape and used to replace the damaged part of Castillo’s airway. Four days later the grafted part of the airway was largely indistinguishable from the natural surrounding tissue. Today Castillo can walk up stairs, play with her children and look forward to working and leading a normal healthy life.

Most remarkably of all, Castillo has not been required to take any immunosuppressant drugs. Cells grown from Castillo’s own stem cells populated the donor organ so her body accepted the donor organ as part of itself and no immune response was launched.

This is only a single case study and the methods might not generalise to solve the problems faced by many other patients. Also, there is still time for the donor organ to face rejection or to fail in other ways. Nevertheless, it is remarkable to have so elegantly avoided the huge problem of rejection; this case study dramatically shows the potential for stem-cell medicine and the collaborative genius of human beings.

There is now the potential to provide many more organs for patients who could benefit but are unable to take immunosuppressant drugs. But this won’t solve the problem of limited donors and it won’t resolve problems posed when a suitable scaffold cannot be created. The obvious solution to these problems lies in the use of cloning technologies and animals.

Cloning procedures involve the nucleus of a cell taken from a patient implanted into a donor egg that is then prompted to grow and divide. After many divisions, a very early-stage embryo develops that will contain stem cells with almost identical DNA to the patient. These cells can be prompted to grow into any kind of tissue – and so can, in theory, combine with small pieces of tissue taken from the patient and encourage growth in that tissue. In this way, entirely new organs can be grown almost from scratch without any need for a scaffold.

An alternative approach is to take adult stem cells from the patient and use those cells to grow tissue on an animal scaffold. There is, for example, great hope associated with the use of pig hearts for human patients, but these xenotransplantation procedures will fail unless the problem of rejection is resolved.

Currently, however, there is much controversy over the use of embryo stem cells and the use of animals as donors. The possibility of US president-elect Barack Obama reversing President George W Bush’s stem-cell policy restricting research to lines already created has led to talk of ‘eugenic human experiments’ and ‘the law of the jungle’ (2). Meanwhile the use of animals as donors is greatly limited by regulations that prevent, for example, the mating of transgenic animals and exaggerated concerns about viral transmission (3).

These concerns unfairly malign the intentions of medical scientists and unnecessarily detract from what could be an entirely new era of regenerative medicine. This is not the 1930s. There is simply no indication or evidence that cloning technologies will be mobilised for nefarious purposes. And while it is always possible for things to go wrong, it is anti-human and anti-rational to pit what we don’t know as being of equal worth to what we do know. Over the past 15 years, notable effort has been put into finding evidence for viral transmission via xeonotransplants, and no evidence has been found (4).

Professor Paolo Macchiarini and his colleagues have demonstrated what our capacity to investigate and understand can provide. Complementary work with embryonic stem cells and animal donors is predicated on the same capacity for reason and we should celebrate the increased opportunities and breakthroughs available. The dramatic success with Castillo is part of a more human world where ignorance does not condemn people to premature death.

Dr Stuart Derbyshire is a senior lecturer at School of Psychology at the University of Birmingham, England.

(1) ‘Clinical transplantation of a tissue-engineered airway’, the Lancet, 19 November 2008

(2) Opponents brace for end of stem cell ban, USA Today, 17 November 2008

(3) Breeding pigs for organ transplants, BBC News, 8 September 2008

(4) ‘Search for cross-species transmission of porcine endogenous retrovirus in patients treated with living pig tissue’, Science 1999; 285: 1236-1241