Researchers "Grow" New Blood Vessels
The synthetic vessels can be stored for long periods and avoid the complications typical of vessel grafts.
Synthetic blood vessels that can be made in advance and stored until surgery could help patients undergoing heart surgery, hemodialysis—cleansing of the blood in cases of kidney failure—and other procedures. Laura Niklason, an anesthesiologist and biomedical engineer at Yale University, and her collaborators have grown blood vessels using human cells and tested them in baboons, showing that they provoke no immune rejection and avoid common complications of synthetic vessels, such as clotting, bursting, or contracting over time. Researchers hope these studies will show that the vessels are safe enough to win permission from the U.S. Food and Drug Administration to begin clinical trials.
During bypass surgery, doctors looking to circumvent blocked arteries usually harvest vessels from a patient’s leg or arm. But people who suffer from vascular disease or who have had previous procedures may have no suitable vessels left. The other options have complications: grafts from donors are often rejected by the recipient’s immune system, artificial plastic vessels have high rates of blood clots and other problems, and vessels grown from a patient’s own tissue take more than six months to mature. “Artificial grafts suffer from clotting and obstruction because they are not tissue,” says Niklason, especially when plastic is used.
Niklason says she has solved this problem by creating vessels that are derived from living tissue but can be used off-the-shelf and are not rejected by the immune system. Using a technique she developed at MIT in the 1990s, researchers seed tubular scaffolds with smooth muscle cells. The cells secrete collagen and other connective tissue molecules around the scaffolds, forming blood vessels. After the scaffolds break down, the vessels are washed with a detergent that strips away the cells, leaving behind the fibrous tubes of collagen.
Because the tubes contain no living cells, they do not trigger an immune response and have a shelf life of more than a year. The group has previously grown vessels using cells from several different animal species, including canine versions for heart bypass surgeries in dogs.
Now, in a report published in Science Translational Medicine, the researchers have grown vessels using human cells for the first time. They used the vessels to link an artery and a vein in baboons, creating a structure called a fistula to mimic the setup required by hemodialysis patients, who have a needle injected into such a link two or three times a week to get their blood filtered. Also, while previous versions of the vessels required a wait of several weeks while the insides of the vessels were “personalized” with some of the patient’s own cells, a process that makes them less likely to clog, these hemodialysis vessels did not need that treatment.
“That means they could potentially be immediately available to the patient,” says Shannon Dahl, a biomedical engineer who cofounded a biotechnology company called Humacyte with Niklason and another colleague to help bring the technology to market. Humacyte initially plans to test its technology in hemodialysis patients, though Dahl declined to give a timeline for clinical trials.
Researchers ultimately hope to test the vessels for heart surgeries, but they first want to show that the technology is safe and effective. “I would love to get to coronary bypass at some point, but we have to prove that this is a good, safe therapy in other anatomical locations first,” says Niklason. A hemodialysis graft is much more easily replaced than a bypass graft if there are infections or other problems.
The researchers’ use of baboons also provides important additional support before they move into human trials, says David Putnam, a chemical engineer at Cornell University who studies biomaterials. The reason is that the dynamics of blood flow in baboons are a good model for what happens in humans, he says. “They are going about this very well, very carefully. They’re building a house with very strong bricks,” he says. “And the next step is humans.”