Steve Connor and Jeremy Laurance
Surgeons crossed another medical frontier this week with the transplant of a windpipe grown from stem cells – the “mother” cells of the body capable of developing into specialised tissue. The success of the operation in Barcelona on Claudia Castillo, a 30-year-old mother-of-two, proved what scientists have long promised – that stem cells can now be used to fashion replacement body parts.
The success of the medical procedure has opened the door to other possible breakthroughs in regenerative medicine – which is when damaged body parts are repaired in situ rather than being removed and replaced by whole organ transplants. Medical scientists believe that few body parts will be left untouched by the technical, genetic and surgical breakthroughs that could revolutionise medicine in the 21st century.
British scientists claimed a world first last April after they helped a blind man to see with an injection into the back of the eye. Steven Howarth, 18, from Bolton, who had a rare inherited eye disorder which left him unable to see in low light, improved sufficiently after the treatment to be able to navigate a maze in conditions similar to street lighting at night.
He was one of the first three patients with eye disorders to be treated with gene therapy – an injection of normal versions of the defective gene that caused his condition, Leber##s congenital amaurosis. Scientists at Moorfield hospital, London, said it would lead to other eye treatments.
Claudia Castillo made history as the first patient to receive a whole organ transplant grown using her own stem cells and without the need for powerful anti-rejection drugs.
Surgeons used a windpipe from a donor which they stripped of all living cells and re-seeded with cells grown in the laboratory from Ms Castillo##s bone marrow. The transplant was carried out last June and blood tests have shown no sign of rejection.
American specialists announced a breakthrough in 2006 by growing parts of new bladders in the laboratory from patients## own stem cells and successfully implanting them. Seven patients given the new bladders had functioning organs that performed as well as those conventionally repaired.
The breakthrough demonstrated the potential of regenerative medicine – growing your own tissues and organs.
Scientists at the Institute for Regenerative Medicine in North Carolina, where the operations were carried out, are working on 20 tissues and organs, including blood vessels and hearts.
The procedure involved taking cells from the patient##s bladder, which was grown on a biodegradable “scaffold”After eight weeks, it was used to patch the damaged organ. The repaired bladder was working well up to seven years later, when the breakthrough was announced.
Chronic wounds are already treated by grafting pieces of the patient##s own skin, which is usually taken from the thigh, onto the affected area. However, this can result in unsightly scarring at two places on the body.
Another technique being developed is to grow skin – dermal tissue – in the laboratory using adult stem cells extracted from the roots of hairs plucked from the back of the scalp. Scientists can grow numerous small patches of skin using this technique. These skin patches can then be transplanted on to the wounded area to regrow the skin over the damaged tissue without scarring or the risk of tissue rejection, which occurs when donor skin is used.
Scientists at the Fraunhofer Institute for Cell Therapy and Immunology in Leipzig, Germany, have been given a licence to grow skin in this way from patients with conditions that result in open wounds, such as leg ulcers.
The Immune System
The body##s defensive system against invading diseases can be regenerated or replaced in a number of ways. One of the most successful is by a transplant using donated umbilical cord blood for children with severe combined immune deficiency (Scid), when they lack the white blood cells of the immune cells produced by the bone marrow.
The transplanted stem cells repopulate the patient##s bone marrow. An alternative is to create embryonic stem cells from a patient##s own skin cells and convert them into the stem cells of the immune system, in which case there would be no need for immunosuppressant drugs.
The Brain & Nerves
In one technique, stem cells are extracted from cloned embryos created from a patient##s skin cells and used to create mature nerve cells that can be transplanted into damaged areas of the brain. Another strategy is to block production of the protein inhibitors within nerve cells that are thought to prevent regeneration.
The world##s first face transplant carried out by French surgeons on Isabel Dinoire in 2005 made headlines around the world. It marked a breakthrough because of the intricate surgery required to reconnect the scores of nerves and blood vessels which supply the face. She had been savaged by her dog after taking a cocktail of drugs in an apparent suicide attempt.
Mme Dinoire, 38, was given a new mouth, nose and chin and the success of the operation was judged in part on how effectively her new face regenerated to restore her sense of identity. Three years on, she admitted she had still not come to terms with her new face which was “not hers, it##s somebody else##s”.
Doctors at the Royal Free Hospital, London, have been given ethical permission to carry out a further face transplant and hope to refine the technique.
French doctors unveiled the latest version of the mechanical heart last month, which is claimed to beat almost exactly like the real thing. Made of titanium and animal tissue, the device uses electronic sensors to regulate the heart rate and blood flow and is even said to fool cardiologists when they are shown its ECG trace.
Existing artificial hearts are designed as a stop-gap, to help people over transplant operations or while they are waiting for a new organ. In some cases they are used to “rest” the patient##s own heart, to give it time to recover from infection or disease until it is ready to take over its function as the body##s main pump circulating the blood.
British patients have been implanted with artificial hearts for up to two years, before having them removed and allowing their own hearts to pump again.
Doctors have been seeking a treatment for diabetes for decades that avoids the need for daily injections of insulin. Since 2000, a dozen patients have received transplanted islet cells, the insulin-producing cells in the pancreas, from dead donors which have worked with varying degrees of success. The Department of Health agreed this year to fund further research, involving 80 patients annually.
Japanese doctors took the treatment a stage further by carrying out a live transplant, from a mother to her 27-year-old daughter. A section of the mother##s pancreas was removed, the islet cells isolated and washed and infused into her daughter##s liver, where they began functioning normally, producing insulin.
Scientists at Akron University in Ohio are experimenting with a “bio-artificial” pancreas – the size of a cigarette coated with a membrane that holds islet cells and promotes the exchange of insulin and glucose between the cells and the blood.
The Ovaries and Testes
The reproductive organs present unique problems. In men, sperm is produced profusely and continuously and can be easily frozen and stored.
Women, however, only produce one or two mature egg cells each month and their reproductive life ends at the menopause. On top of this, egg cells are difficult to freeze. For infertile men and women who cannot produce any sperm or eggs, there is the possibility of creating the sex cells – gametes – in the laboratory from skin cells. The idea is to use the skin cells to create cloned embryos by inserting the cell nucleus into donor egg cells that have had their own nucleus removed.
After extracting embryonic stem cells from the three-day-old cloned embryos, scientists hope to stimulate them with nutrients and messenger chemicals to develop into mature sperm or eggs which crucially have half the number of chromosomes as the skin cells from which they were derived. Several research groups have achieved this stage of successful “haploidisation” in animals and are hoping to do the same with human skin cells to produce viable sperm or eggs.
Duchenne muscular dystrophy is caused by a person##s inability to produce a muscle protein called dystrophin. Scientists know how to make healthy versions of the dystrophin gene, and hope to find ways of inserting it into the affected muscles, and thus getting these damaged cells to behave normally. Gene therapy research is also looking at ways of boosting muscle size and strength.