Surgeons from Karolinska University Hospital have carried out the world's first synthetic organ transplant, after scientists in London created an artificial windpipe which was then coated in stem cells from the patient. The procedure required the coordinated efforts of scientific teams in London, Massachusetts and Stockholm, Sweden, where the windpipe was surgically implanted. The artificial trachea was transplanted in a 12 hour surgery led by Dr. Paolo Macchiarini, a pioneer in engineered trachea transplantation, at the Karolinska University Hospital in Stockholm. The patient had been suffering from late-stage tracheal cancer. A rare, aggressive tumor was blocking his windpipe making it hard for him to breath. Diagnosed in 2008, the patient had failed every conventional treatment including chemotherapy, radiation and surgery. He was running out of time, so rather than wait for a donor trachea for transplantation, his doctors suggested growing his own in the lab. The Y-shaped structure was then coated in a special polymer containing millions of tiny hole. The organ consisted of an artificial, trachea-shaped scaffold that had been lined with the patient's own stem cells. The cells take just a few days to grow around the scaffold. Because the organ included the patient's own cells, the patient did not need to take immunosuppressive drugs to prevent a rejection of the organ. Crucially, the technique does not need a donor, and there is no risk of the organ being rejected. The polymer scaffold was made by Alexander Seifalian at University College London. The bioreactor that would hold the trachea and incubate it with patient’s stem cells was created by Harvard Bioscience, near Boston. The scaffold and bioreactor were then shipped to Stockholm, where the solution containing the patient's stem cells was added. The final product was days in the making, versus the months it could have taken to locate a donor organ. In that case, the transplant used part of a trachea from a donor as the scaffold, which was then coated with the patients' stem cells. The patient is now on his way to recovery and will soon be release from the hospital, the researchers said.
The advantage of the synthetic trachea is that no death or donation is needed. "The big conceptual breakthrough is that we can move from transplanting organs to manufacturing them for patients," says David Green, the president of Harvard Bioscience in Holliston, Massachusetts, which provided the technology for coating the synthetic trachea with the cells. "This same concept would work best for simple organs such as tracheas, ureters and blood vessels," says Green. For more complex organs, the donor organ approach might still be better, he says. Key to the synthetic trachea is a novel polymeric nanocomposite material developed at University College London by Alexander Seifalian. "It contains millions of tiny holes so living cells can grow on it," says Seifalian. By altering the recipe, Seifalian can give his polymers a huge variety of properties to suit different organs. The synthetic trachea, for example, has tough, durable rings mimicking the cartilage rings in real tracheas, separated by much softer, flexible materials which allow the artificial trachea to bend, just like a real one. Seifalian custom-built the trachea to match the dimensions of the patient's own, which was due to be removed because it was occupied by a large cancer. Two days before the operation, the researchers took 200 millilitres of bone marrow, extracting from it around 40 millilitres of the mesenchymal stem cells for coating the artificial trachea. The researchers poured the stem cells over the trachea as it was rotated about its axis within a bioreactor the size of a shoebox. The organ was half-covered with fluid containing nutrients and the patient's cells, and as it rotated, it was exposed to air, giving the cells the oxygen they needed to survive and grow. No extra growth factors were needed to make the stem cells change into tracheal surface cells, because the trigger to do this was the shear stress they experienced as the trachea moved against the surrounding fluid. Before Macchiarini implanted the trachea, he took slivers of cells lining the patient's nose and deposited these on the inside of the trachea, where they would eventually coat the entire inside surface with epithelial cells, as they do a normal trachea. In the past two years, researchers have used similar stem cell therapies to make ureters and larynxes.