Heart Disease News (dateline April 16, 1999)
Dr. Laura Niklason, a researcher at Duke University, has grown artificial arteries in the lab using cells from pigs and has successfully implanted the vessels back into the animals. These arteries, unlike synthetic vessels, are the more appropriate size and strength needed for heart bypass operations and are less likely to clog. Dr. Niklason's discovery was published in the journal Science on April 16, 1999.
This development has significant implications for heart bypass surgery. Researchers consider this a major step in the developing field of tissue engineering, where scientists are trying to build viable artificial organs in the lab. "We're growing arteries in a way that simulates the environment in the fetus when arteries normally develop," Dr. Niklason said, explaining that the arteries take eight to 10 weeks to grow. "Hopefully, this lays the groundwork for doing it in a patient."
Christine Schmidt, an expert in engineering artificial blood vessels at the University of Texas in Austin, said researchers have been trying for more than a decade to do what Niklason has managed. "Artificial arteries are what we consider the Holy Grail in the field," Schmidt said. "It's important because ... there's not a good artificial alternative for small-diameter arteries right now. For many years, people have tried synthetics, and they don't work."
Well over 600,000 patients a year in the United States and internationally receive coronary bypass operations, according to the American Heart Association. During a coronary bypass procedure, doctors take a vein (typically from the patient's leg) and graft it in place of a clogged or diseased coronary artery. The grafted vessel routes blood around the blockage in the diseased artery that is no longer properly feeding blood to the heart muscle (myocardium). In normal use, veins are not as strong as arteries since they only have to carry blood at a lower pressure. Thus, veins grafted in place of arteries (especially the coronary arteries) can be damaged from the higher pressure they receive when being used as arteries. In addition, some patients may suffer complications from the loss of veins in their legs, and other patients don't have veins in good enough condition for the bypass graft.
Dr. Niklason decided to get involved in tissue engineering while finishing her residency at Massachusetts General Hospital in Boston. She approached Robert Langer, a professor at the Massachusetts Institute of Technology, about joining his research lab. She chose artificial arteries as her first project. Dr. Niklason likes to experiment and felt tissue and blood vessel engineering was a task worth tackling. "When I started this project, there were a lot of things I didn't know. ... I didn't know how cells grow and behave in the lab," Dr. Niklason said. "But I figured I have a good general background in medicine and fluid dynamics, so I could figure it out."
Niklason toiled with very few results for months. She took muscle cells from the outside of pig arteries and set them growing on a tube-shaped synthetic scaffold. The idea was that as the cells reproduced, the scaffold would dissolve, leaving a finished artery. Two years into the project, the best she could create was an artery that would fall apart at the touch of tweezers. "I had failure after failure after failure. It was pretty discouraging," Niklason said. Eventually she created a device that helped the artery grow thicker and produce collagen strands to make it stronger. A mechanical pump forces red cell culture liquid through the artificial arteries at a rate of 160 beats a minute, the same rate at which the heart of a fetus pumps and twice that of an adult heart.
Dr. Niklason promotes collagen growth by feeding the arteries each day with vitamin C. She adds intermittent blue ultraviolet light that kills bacteria, since arteries developed in a lab have no way of staving off infection. When the vessels are nearly grown, she applies a different cell from the inside wall of a pig artery to the artificial vessel. This last stage is critical to prevent clotting once the vessel is implanted. The results are small, grayish white tubes with the elasticity of real arteries. They respond to drugs much the same way that real arteries do. When the vessels were implanted in pigs, they stayed free of clots for four weeks. Comparable vessels that were grown without liquid being pumped through them began to clot much sooner.
The next steps: study the vessels over a longer period and eventually try to replicate the research with human vessels
The next round of research will be to show what happens with the vessels over a much longer period. "She's pushed things several steps beyond where they were before," said Langer, a pioneer in tissue engineering. Niklason did much of her work in Langer's MIT labs. "Previously most people had tried to grow arteries in static conditions rather than design something that simulated the heart," Langer said. Niklason brought her device and her research with her when she moved to Duke University to take over a lab in September 1998.
While Niklason's research points a direction for doing the same thing in humans, it could take years to develop a working model. Human cells do not grow in the lab as well as pig cells. And cells from older people, those most likely to need bypass operations, are even more difficult to grow. "There's no fundamental reason why it shouldn't work," Niklason said. "But in research you learn not to guarantee anything."