Off-the-shelf blood vessels
Heart bypass patients may soon be able to get new arteries without having to sacrifice vessels from other parts of their body, thanks to ready-made, off-the-shelf artificial blood vessels.
Biomedical engineers have been trying to build replacement blood vessels, needed for coronary artery bypass surgery and kidney dialysis patients, for three decades. Researchers from Humacyte Inc., in Durham, N.C., discovered the trick: recruiting cells to build the vessel, then washing them away so the nonliving tissue is storable and works for anyone. The team reported their findings in the Feb. 2 issue of the journal Science Translational Medicine.
Humacyte’s methods are the first to yield ready-to-use vessels that could be suitable for emergency surgery. The company estimates that, annually, 100,000 Americans who need bypass surgery don’t get it because they have no suitable replacement.
The company has managed to make a “universal blood vessel,” says Gordana Vunjak-Novakovic, a biomedical engineer at Columbia University in New York who was not involved in the study. “This is very practical and convenient for clinical applications.” Other approaches, customized with a patient’s own cells, take several months to prepare.
Though Humacyte is starting to plan human clinical trials, it’s too early to predict when the grafts would become available to the general public.
When performing bypass surgery — in the heart or elsewhere in the body — surgeons need replacement vessels that match the size of the old ones. Often they can harvest vessels from elsewhere. Two mammary arteries in the chest and a pair of veins from the legs can often get the job done.
Most self-to-self transplants perform quite well, says Dr. Alan Kypson, a heart surgeon at the East Carolina Heart Institute in Greenville, N.C., who co-authored the Humacyte report. But if a person has varicose or swollen veins, or needs multiple bypasses, the body’s own vessels may not be sufficient, he adds.
Plus, these transplants are a case of “robbing Peter to pay Paul,” says Yadong Wang, an associate professor of bioengineering at the University of Pittsburgh who also works on artificial vessels (see the related article). Removing the vessels lengthens time in the operating room and causes pain and swelling that can last up to six months.
Artificial vessels could also be useful for people on kidney dialysis machines. To get easy access to fast-moving blood, doctors typically link an artery and vein, making an artificial shunt. But that structure can withstand only so much poking and prodding; eventually a replacement will be necessary. Once a person runs out of his or her own vessels, artificial options exist, but they typically last for less than a year.
To build a better vessel, the researchers collected smooth muscle cells from the aortas of cadavers. They put the cells in a polymer tube that acted as a scaffold. To make the environment more like a natural vessel, they pumped fluid through the tube, mimicking blood flow.
Over time, the scaffold degraded as the cells did their work. The cells produced a network of proteins such as collagen, which gives blood vessels their strength. After seven to 10 weeks, the scientists washed away the cells, leaving behind a clean, ready-to-use artificial vessel.
“All we’re left with is the proteins the cells have secreted,” says Shannon Dahl, co-founder and senior director of scientific operations at Humacyte, who led the study. With no cells, there’s no worry that the patient’s immune system will attack the graft. And, she adds, the graft is not really “living,” which explains why it can last so long in the refrigerator.
About 5% to 10% of bypass surgeries are emergencies, Kypson says; other patients can afford to wait for days or weeks. Off-the-shelf grafts would be a boon for all patients, though, since it would mean shorter surgeries with quality-controlled, size-matched transplants.
A new blood vessel has to withstand the heart’s constant pumping. In a healthy person, blood pressure tops out at approximately 120 millimeters of mercury. In tests, Humacyte’s vessels could withstand a burst of more than 2,000 millimeters of mercury. They won’t pop.
Kypson tested artery-vein shunts in nine baboons; the shunts lasted for at least six months. The scientists have not yet tested the vessels for longer periods.
He also tested coronary artery bypass replacements in five dogs. The vessels all lasted for at least a year. The scientists have not yet completed longer-term experiments, so the maximum lifetime of the grafts is unknown.
Dahl does not yet know how much the grafts would cost, but anticipates it will be less than the $15,000-and-up for personalized grafts from patient’s own cells. The company can use cells from multiple cadavers to generate hundreds of grafts at once, making production much cheaper.
Humacyte’s protocol is a major advance, says Robert Tranquillo, a biomedical engineer at the University of Minnesota, Twin Cities, who was not involved in the study. However, he adds, it is not yet known if the cell-free vessels will eventually degenerate in the body.
Scientists are pursuing several ways to grow vessels, and the best method remains uncertain, Tranquillo says. He notes that a company called Cytograft is also trying grafts made from patients’ own rolled-up skin cells. There is plenty of testing left to do, in terms of safety and effectiveness of the transplants.
