World first as woman gets organ made from stem cells

A WOMAN has become the first patient in the world to receive an organ created in a laboratory, in a pioneering operation that could change transplant surgery, doctors said yesterday.

Claudia Castillo's body part was grown using her own stem cells harvested from bone marrow.

Professor Anthony Hollander, part of the team behind the breakthrough, described it as an example of "stem cell science becoming stem cell medicine".

Using Ms Castillo's stem cells to create a new airway for her means there are none of the tissue-rejection problems that are a major issue for transplant surgery and which usually mean recipients have to take powerful drugs for the rest of their lives.

Researchers from the UK, Italy and Spain worked together in the extraordinarily complex procedure to grow tissue from the 30-year-old mother of two to fashion a new bronchus – a branch of the windpipe – and carry out the transplant operation.

Scientists believe the same approach will be used in years to come to create engineered replacements for other damaged organs. In five years, they hope to begin clinical trials in which laboratory-made voice boxes are implanted into patients with cancer of the larynx.

Professor Martin Birchall, a member of the team from the University of Bristol, said: "What we're seeing today is just the beginning. This is the first time a tissue-engineered whole organ has been transplanted into a patient.

"I reckon in 20 years' time, it will be the commonest operation surgeons will be doing. I think it will completely transform the way we think about surgery, health and disease."

He predicted the technique could be applied to other hollow organs similar in structure, such as the bowel, bladder and reproductive tract.

Colombian-born Ms Castillo, from Barcelona, Spain, had suffered a serious tuberculosis infection that ravaged her airways, leaving her short of breath and unable to carry out the simplest tasks.

Disease had caused her windpipe, or trachea, to collapse at the point where it entered her left lung.

A series of complex steps pushing the boundaries of medical science led to the transplant operation, performed on 12 June by Professor Paolo Macchiarini at the Hospital Clinic of Barcelona.

A section of windpipe was taken from a female donor who had died and the trachea was stripped of its cells, leaving only connective tissue. Stem cells from Ms Castillo's bone marrow were then grown in the laboratory. Next, the donor trachea had to be "seeded" with two different kinds of cells – those made in the laboratory and those derived from tissue taken from Ms Castillo's nose and healthy airways.

The trachea graft was placed into a rotating "bioreactor" and the machine allowed the cells to migrate to the correct locations, where they began to grow naturally.

Finally the trachea, now covered in cartilage and lined with cells all bearing the patient's own genetic hallmark, was cut to shape and slotted into place. Without the pioneering operation, the lung would have had to be removed.

Today, Ms Castillo is living an active, normal life, and is once again able to look after her children, Johan, 15, and Isabella, four. Yesterday, she said: "I was scared at the beginning because I was the first patient but had confidence and trusted the doctors. I am now enjoying life and am very happy that my illness has been cured."

So far, doctors have seen no sign of her immune system rejecting the transplanted organ, even though she received no immunosuppressive drugs.

Prof Birchall admitted the decision to turn to tissue engineering to help Ms Castillo had been a "leap of faith" and the same procedure had only been attempted on pigs before.

Details of the transplant were described in a online edition of The Lancet journal.

Prof Macchiarini said: "We are terribly excited by these results. Just four days after transplantation, the graft was almost indistinguishable from adjacent, normal bronchi."

Dr Allan Kirk, from the American Society of Transplantation, said: "They have created a functional, biological structure that can't be rejected."

However, Dr Josh Brickman, from the Institute for Stem Cell Research in Edinburgh, urged caution. "It is fantastic that they have been able to do this with her own stem cells, which means there is no risk of auto-immune rejection. However, the application to other organs could be difficult," he said.

Sue Pearson, from the Transplant Trust, said: "This is great news, but we don't want to give false hope to people who are waiting for organs. We're sure that this will come to fruition in the future. In the meantime, we would encourage people to sign on to the organ donor register and talk to their next of kin."

Scientists are already looking to the future and seeking European Union funding and commercial sponsors for the more ambitious larynx trials.

Up to 60,000 people a year are diagnosed with cancer of the larynx in Europe, about half of whom may be suitable for tissue engineering transplants.

Since the larynx is a complex organ containing the vocal cords, engineering one from stem cells will be a major challenge. But Prof Birchall said the first trials could take place in about five years.

Professor Martin Birchall - 'I think it will completely transform the way we think about surgery, health and disease'

How the procedure works

1 A section of windpipe, or trachea, was taken from a 51-year-old woman donor who had died, to provide the scaffold or "matrix" around which the new bronchus would be built.

2 Using a pioneering technique involving detergent and enzymes, the trachea was stripped of its cells, leaving connective tissue. The process removed almost all the material that could trigger an adverse immune reaction.

3 Stem cells from the patient's own bone marrow were then grown and multiplied in the laboratory, and treated with "growth factor" chemicals to turn them into cartilage cells called chondrocytes.

4 Stem cells are immature cells with the ability to develop into many kinds of tissue given the right chemical instructions.

5 The 7cm-long donor trachea had to be "seeded" with two kinds of cells – the chondrocytes made in Bristol and specialised epithelial cells derived from tissue taken from the patient's nose and healthy airways. The epithelial cells line the inside of the tracheal tube and carry tiny hairs or cilia for moving debris out of the airway.

6 The seeding process was carried out by placing the trachea graft into a rotating "bioreactor" developed at the Polytechnic of Milan in Italy. The machine allowed the cells to migrate to the right locations, where they began to grow naturally.

7 Finally the trachea, now covered in cartilage and lined with epithelial cells all bearing the patient's genetic hallmark, was cut to shape and slotted into the gap left by the diseased and collapsed bronchus.

Overcoming the problems of immune rejection by using a patient's own cells is a major breakthrough

THIS work is important because it demonstrates how tissue engineers can work together with stem-cell biologists to produce material from a patient's own cells that will not be rejected by their immune system.

To produce something that can be surgically implanted and – so far as we know – not suffer any complications is really quite remarkable.

To get over the problem of immune rejection by being able to use the patient's own cells is a major breakthrough in its own right in terms of transplant.

At the moment, this cannot be used on a huge scale because it is such a patient-specific treatment, but it is a wonderful demonstration of the fact that stem cells can be used in this way and to the benefit of patients.

I can see a time when a treatment like this will be used on the NHS in specific disease cases.

The research is a major step forward to realising regenerative medicine. It is certainly important and one more step along the way. We are not yet where we aim to be in regenerative medicine, but this is helping us get there.

In terms of the developments being made in stem-cell research at the moment, we have a number of clinical trials using treatments based on adult stem cells under way in the UK. There are even more under way in the United States.

The theory has always been there to use adult stem cells and expand them into more than just blood stem cells.

It will lead to potentially more surgeons trying this sort of surgery and using tissue engineers alongside stem-cell biologists to create parts of organs that can be transplanted. This is a procedure that is risky. It does not have any guarantees, and no doubt this patient has been very bold and gone through with it because she has confidence in the doctors and the surgeons.

Patients who are suffering from chronic conditions should be able to look at this piece of work and make their own mind up based on the risk.

If they see in the longer term, as I hope it turns out, that this patient has improved quality of life and for a long period of time, then that ought to encourage others to try this sort of surgery through their own doctors.

It is always important that we have patients who are willing to take part in clinical trials.

One issue in progressing with stem-cell research is having the patients who will enter into this kind of work. This is one of the issues that the network will be discussing at a meeting in London next week.

Though we may be cautious while we await the longer-term results, all the signs are there that this is a tremendous piece of research and surgery.

I think it is a major advance and hugely encouraging in our aim to develop regenerative medicine further.

• Ben Sykes is co-ordinator of the UK National Stem Cell Network.