Starting with bits of skin, scientists have produced new blood vessels in a laboratory and successfully implanted them into two patients, a medical first.
Previously, vessels grown in a lab had failed to hold together without the support of a synthetic backing. Unfortunately, backing materials such as plastic aren’t flexible enough to handle the variable pressures of blood flow. Also, some backings trigger inflammation and attract blood clots.
Researchers at Cytograft Tissue Engineering in Novato, Calif., have created vessels from a patient’s own cells, an approach that avoids inflammation, clot formation, and immune rejection. Surgeons in Argentina installed the engineered vessels in place of artificial shunts in the arms of two kidney-dialysis patients. In the 6 months since the operations, the new vessels have worked well, say the Cytograft scientists. They announced their findings last week at a meeting of the American Heart Association in Dallas.
The team now plans to test the vessels in more kidney patients and eventually in heart patients. The Cytograft researchers hope to get the procedure approved for coronary-bypass surgery in about 5 years.
The scientists start by taking immature cells called fibroblasts from a patient’s skin and growing sheets of the cells in lab dishes. Each sheet is about the size of a postcard. They roll each sheet around a tube the diameter of a narrow drinking straw. Finally, they withdraw the tube and seed each nascent vessel with cells taken from the lining of one of the patient’s blood vessels.
In 6 months, the process can create vessels 17 centimeters long and nearly a half-centimeter in diameter, says cell biologist Nicolas L’Heureux of Cytograft.
The group is testing the vessels in dialysis patients first because arm surgery poses fewer risks than a heart-bypass operation.
Dialysis, which cleans a patient’s blood, requires the direct flow of blood from an artery to a vein in a surgically produced connection called a fistula or a synthetic connection called a shunt. Needles inserted into a fistula or shunt divert blood under high arterial pressure into a filtration device. However, fistulas and shunts often clog or become infected.
The two dialysis patients using the tissue-engineered vessels have been free of complications during the 6 months since surgery, says biomedical engineer and head of Cytograft Todd McAllister. “This is the first-ever human use of a tissue-engineered blood vessel in high-pressure arterial circulation,” he adds.
Previous lab attempts to grow functional blood vessels included smooth muscle cells, which are integral to natural-vessel architecture. Those efforts failed because the cells are difficult to keep alive, L’Heureux says. In contrast, fibroblasts thrive.
The cells added from vessel lining produce anticlotting factors that keep blood moving, says heart surgeon Timothy J. Gardner of Christiana Care Health Services in Newark, Del., who isn’t associated with Cytograft.
Even with lining cells included, vessels grown on synthetic scaffolds “have been disappointing,” he says. “They don’t act like blood vessels,” which need to be flexible to handle the fluctuations in pressure that go with heart exertion and relaxation. The new approach “is a terrific design,” he says.
“This is an exciting advance for sureâ€”if it works” over the long term, says heart surgeon Richard D. Weisel of the University of Toronto. “Anything is going to be better than the synthetic materials we have now,” he says.