By Tiffany O'Callaghan
Small-scale animal studies suggest that surgeons might one day be able to simply open the refrigerator when the need for patient-ready bioengineered blood vessels presents itself.
Patients with coronary artery disease or peripheral arterial disease are often treated with bypass surgeries -- in which the blood vessel that has narrowed as a consequence of the illness is closed off and circumvented by the implantation of an unrestricted 'conduit'. To avoid complications, surgeons prefer to use vessels taken from a patient's own body -- harvesting a portion of vein from the leg, for example. But alternatives are often necessary for patients who have had to go under the knife many times, or who merely lack enough robust blood vessels.
Current alternatives have different limitations. Synthetic blood vessels made from polytetrafluorethylene only last for a median time of about 10 months before their flow is reduced as a result of complications such as infection or clotting. Meanwhile, the risk of hardening, clotting and aneurysm has limited the use of grafts taken from human cadavers.
One particularly promising option has been the development of tissue-engineered vascular grafts, which are made using a patient's own cells -- limiting the likelihood of rejection. However, these types of patient-specific grafts take up to 9 months to grow and can cost more than $15,000 per vessel.
Now Shannon Dahl, co-founder of biotechnology firm Humacyte in Durham, North Carolina, and her collaborators have developed a way to grow 'bioengineered veins' from donor cells by introducing the cells into scaffolds made of polyglycolic acid. Once these vascular grafts have grown in a bioreactor, the team strips them of cellular material using specialized detergents, leaving collagen tubes that are non-immunogenic -- that is, unlikely to be rejected by patients' immune systems. Using this method, the researchers say that instead of making one vascular graft at a time with one patient's cells, they could use cell banks to make as many as 37 large or 74 smaller blood vessels per donor, and cell banks put together from multiple donors could hold even more.
"We think we might be able to provide an alternative where other products don't function very well or aren't available," says Dahl. The research is published today in Science Translational Medicine.
The researchers tested the strength and durability of the bioengineered veins after they had been stored in a saline solution in the refrigerator for a year. When tested for burst pressure and other factors, the vascular grafts demonstrated characteristics similar to those of human blood vessels.
The team also implanted vascular grafts constructed from human donor cells into baboons. In the three baboons followed for six months, checks at 1, 3 and 6 months found that the 6-mm-wide bioengineered vessels remained open to the flow of blood, or 'patent'. In the five baboons followed for 1 to 3 months, all but one bioengineered vessel remained patent.
In a final experiment, the researchers used cells obtained from dogs to engineer narrower 3-mm-wide veins using the polyglycolic matrix. Narrower blood vessels that aren't native to a patient's own body tend to fail much more often than wider ones. The team seeded the grafts with the dogs' own endothelial cells, which line the interior of blood vessels. For five out of six dogs in the study, the bioengineered blood vessels remained active when checked at selected intervals -- with the two cases checked after a year still showing patency.
However, Edward Woo, vice-chief of vascular surgery and endovascular therapy at the University of Pennsylvania in Philadelphia says that until the team carries out longer follow-up studies with more animals, little can be said about the long-term patency of the bioengineered veins. "Their data are pretty weak," says Woo. "I think it is interesting, this extracellular matrix that can be refrigerated, but they have not proven in their study that there's any improved patency of this over anything else that's out there right now."
Gianni Angelini, clinical chair of cardiothoracic surgery at Imperial College London, says that if the smaller blood vessels made by the team need to be seeded with a patient's own cells, that would reduce the "off the shelf" utility of the grafts.
Dahl concedes that this is a major point to address in future research. "Maybe in the future it could be possible to use a bioengineered graft without endothelial cells, but that remains to be seen," she says.