Reposted from:
http://www.telegraph.co.uk/scienceandtechnology/science/sciencenews/3486000/Transplant-of-windpipe-grown-from-stem-cells-heralds-new-era-in-medicine.html
and
http://www.huffingtonpost.com/2008/11/19/organ-grown-from-stem-cel_n_145049.html



The transplant of a human windpipe grown from stem cells is a surgical breakthrough of almost limitless potential

The science of healing is developing so quickly that it has become almost a cliché to describe a particular operation as a "breakthrough". Yet there is no doubt that the first successful transplant of a human windpipe, constructed partly from stem cells, is an astonishing milestone – one that could indeed mark the start of a new era in medicine.

At long last, the glint in a researcher's eye has been turned into a significant advance in the clinic. Forget all the fuss about embryos and angst about playing God: this is unadulterated good news. We have proved that scientists can now fashion organs using a patient's own cells, eliminating the problems with rejection that have always plagued transplants. Today it is a trachea – tomorrow it could be a colon, even a heart.

The venture was a textbook example of international collaboration, drawing on the talents of teams in Spain, Italy and Britain. To recap; the operation, on 30-year-old tuberculosis patient Claudia Castillo, took place in Barcelona, where doctors also had collected a three-inch segment of trachea from a 51-year-old donor who had died of a cerebral hemorrhage. They used a technique developed in Padua to strip the windpipe of its donor's original cells, a procedure that took six weeks, to create a "scaffold". At the same time, a team in Bristol used a "bioreactor" dreamt up in Milan to grow stem cells removed from Castillo's bone marrow. These cells were "seeded" into the donated windpipe, disguising the 'foreign' tissue that remained so Castillo's body would accept it as her own.

There is a desperate need for this kind of advance. In Britain, about 8,000 people are on the waiting list for an organ transplant. Around 3,200 such operations are carried out every year – but roughly 1,000 of those on the list will die before they get a transplant. And that is only the start of the problem: after a transplant, there is a high risk of rejection as the recipient's immune system reacts against the donor organ. Immunosuppressant drugs are used to limit this but their side-effects include high blood pressure, diabetes and kidney failure, vulnerability to infections, osteoporosis, and cancer. In all, the drugs cut life expectancy by an average of 10 years.

As we now know, Claudio Castillo experienced no such problems: two months after the surgery, which took place in June, her lungs were functioning just as well as those of most young women her age. The result, says Martin Birchall, professor of surgery at Bristol University, leaves us "on the verge of a new age in surgical care". But what will that new age look like? Even before this week's announcement, there has been a steady trickle of advances that reveal the potential of this medical revolution. There are attempts to free insulin-dependent diabetics from reliance on needles, by using injections of their own stem cells. Trials are under way in Britain on more than 90 patients to test the use of stem cells to help repair damaged hearts. Prof John Martin of University College London who is leading the project, says things are "going well".

We can now routinely grow replacement skin (used to aid wound healing), using the foreskins of newborns, while Dr Anthony Atala, of the Institute for Regenerative Medicine at Wake Forest University in North Carolina, has made and successfully implanted segments of bladder in seven patients, aged between four and 19, who had a congenital birth defect.

Dr Atala's technique is a variation on that used to create Claudia Castillo's new windpipe. He began by taking biopsy samples of muscle cells and the cells that line the bladder walls. These were multiplied in the laboratory until there were enough to seed a special biodegradable "scaffold", shaped like a bladder, on which the cells could hang. About eight weeks after the biopsy, the "engineered" patches were sewn on to the patients' original bladders, dramatically improving their function.

The significance of the new work, however, is that the pan-European team was able to transplant an organ, albeit just a section of it. The implications are staggering: given that stem cells from bone marrow can be grown into any one family of tissues, such as muscle, bone, skin and cartilage (though not mucosal or nerve tissues), the team at Bristol University believes the same approach will allow it to recreate colons and bladders, too. With funding, Prof Birchall says that he hopes to engineer a larynx for transplant within five years.

The liver will be trickier. The plumbing and cells involved are intricate and the result of an equally complex series of stages of development. The process is further complicated by the fact that the liver also needs to have blood pumping through it at high pressure and volume to work properly. Even so, the science-fiction vision of organ farms in which spare body parts can be plucked off the rack may not be so far-fetched. "I do believe the various issues are soluble," said Prof Birchall, though he is reluctant to speculate on precisely when.

In much of this work, Europe is leading the way. "By putting our brains together," says Prof Martin, "we are ahead of the US in the clinical application of stem cells."
But remarkable work on the other side of the Atlantic is raising the possibility that the development of a replacement heart is closer to fruition than previously hoped. In January, the world's first beating, retooled "bioartificial heart" was unveiled by researchers at the University of Minnesota, an achievement that could pave the way for new treatments for the 22 million people worldwide who live with heart failure.

While there had been advances in growing heart tissue in the lab, the problem has been how to create a three-dimensional scaffold for the new cells that mimics the complicated architecture and intricacies of the body's circulatory system. That is why Prof Doris Taylor and her team in Minnesota resorted to "decellularisation": using detergent to remove all of the cells from an organ. In this case, they used the heart from an animal cadaver, leaving only the framework between the cells intact, along with the essential plumbing and heart valves.
After successfully removing all the cells from rat hearts, the researchers then took immature versions of those cells and introduced them to the decellularised heart scaffolds. Four days later, contractions were observed, and eight days later the new, partly artificial hearts were pumping, albeit at only two per cent of the efficiency of an adult heart.

Professor Taylor says that she is thrilled by the news of the trachea transplant. "We congratulate the Bristol team wholeheartedly – so to speak – and are excited to see this add credence to the technology used by our group in its research, and others around the world." The method, she believes, can be extended to virtually any organ with a blood supply: "We have made significant progress showing the utility of decellularisation for a number of organs including livers, muscle, skin and kidneys, and are well on the way to building complex new organs." Her own team is tackling the problems involved in rebuilding the vessels in the heart – critical if you are going to engineer something with a blood supply.

And then there is the astonishing potential of embryonic stem cells, the means by which Mother Nature fashions our entire bodies. Our understanding of how to guide the development of an embryonic stem cell is primitive – but unlike the bone marrow cells used in the Castillo case, embryonic stem cells can turn into any one of the 200 or more different cell types in our bodies, rendering the opportunities potentially limitless. As Prof Austin Smith of Cambridge University points out, much more work must be done to determine how to make them grow the right way, and then to mould them into organs. Even so, the potential in terms of replacement body parts – or even replacement bodies – is vast.

The path ahead is difficult: more funding and much testing, will be needed and there will inevitably be false starts and blind alleys. But in the long term, a brave new world beckons, where row upon row of hearts, kidneys and lungs are grown in sterile vessels, ready for transplant. Medically and ethically, the bottom line is simple: if we follow the path blazed by Claudia Castillo and her doctors, no one need ever die waiting for a donated organ again.

• Roger Highfield is the Editor of 'New Scientist'