In a scientific first, biomedical researchers at the University of Minnesota have implanted a section of dead blood vessel in an animal and then watched as it turned into living tissue that grew along with the host’s body for a year.
A team led by U professor Robert Tranquillo said the breakthrough, published Tuesday, could be used to graft tiny sections of lab-grown blood vessels in place of defective arteries in children. Since the grafts would be able to grow inside kids’ bodies just like normal tissue, they could eliminate risky and expensive surgeries that kids with congenital heart defects face later in life.
Just as a pair of jeans doesn’t fit a growing kid after a couple of years, a blood-vessel graft made from plastic or cadaver tissue becomes too small over time — unless it can grow along with the rest of the body. More than 1,000 children a year in the U.S. with heart defects could benefit from such a growing graft.
The experimental work “is focusing, at least at first, on the individuals who are going to get the most out of this device. And that is kids, because they will be able to avoid multiple surgeries they would otherwise have to have down the line,” said Dr. Gwen Fischer, who wasn’t involved in the research directly.
Fischer is director of Minnesota’s Pediatric Device Innovation Consortium, which granted Tranquillo’s team $50,000 for the proof-of-concept project. She said medical device companies locally and nationally have expressed interest in the technology, particularly if it can be used with adults who would make up a more robust market than would pediatric patients.
On Tuesday, Nature Communications, an offshoot of the journal Nature, published the results from Tranquillo’s yearlong experiments that used three young Dorset lambs. Engineers found that after 50 weeks, all three implanted graft segments grew into the expected natural curves, and their diameters and lengths increased to the same degree that the adjacent, natural arteries grew in the same time.
None of the three experimental grafts showed signs of early failure from calcification (tiny bits of bone in the graft) or an immune response that would have caused rejection by the host’s body.
Past work has already shown it is possible to grow a nonliving blood vessel in a lab and then implant it in a human and have it function as a normal vessel would. North Carolina-based Humacyte is running a clinical trial involving 350 people implanted with bioengineered human vessels used for renal replacement therapy.
The work by Tranquillo’s team is new for its growth potential.
“This is the first instance that we know of where a material has been shown to be able to grow with a patient,” Tranquillo said. “For the well-being of the patient, and not to mention the cost involved, there could be really major benefits if this material does in fact grow in a human. We’ve shown it in a sheep, and we would hope that someday it would also be demonstrated in a patient.”
It’s not clear when that would happen. Work is already underway to meet the stringent “good manufacturing process” standards required of all medical devices. Bioethics experts at the U.S. Food and Drug Administration and the U would also have to sign off on any human clinical trial.
Yale University’s Dr. Laura Niklason, founder of Humacyte, lauded the Tranquillo team’s paper as “exciting.”
“I believe the data are compelling supporting growth of a conduit that starts out nonliving, and then becomes populated with cells by the animal that turn it into a living tissue that has growth potential,” Niklason said. She noted the study’s small population size — just three animals — and the fact that the test was a “low-pressure” application, rather than a higher-pressure adult blood vessel in which the mechanical stresses would be greater.
To grow the vascular grafts, Tranquillo’s team purchased sheep skin cells from a lab in New Jersey, combined them with a blood protein and enzyme, and poured the solution into a tubular mold. After two weeks in the mold and another five in a bioreactor, the resulting organic tubes were washed with special detergents to strip away all living cells and remove the possibility of rejection by the donor’s body.
The resulting tube-shaped conduits were made of nonliving extracellular matrix, covered with microscopic holes where the former cells were removed. Though the implanted tubes can carry blood from day one, the cells from the donor’s body populate the implant and allow it to grow like the natural tissue within it.
“For this study we made the tissue tubes from sheep cells and then removed the cells,” Tranquillo said. “We’ve also made these tissue tubes from human cells, and we can remove the cells. Therefore we believe this would also be clinically relevant, in the sense that we can then implant that into a human.”
Dr. Tony Azakie, the chief of pediatric cardiac surgery at the U, said vascular grafts that can grow represent a potential “game-changer” for his patients, about 20 percent of whom are newborns, and another 20 percent are infants.
“I think it’s great that it’s happening at the University of Minnesota,” Azakie said, noting the university’s long history in pioneering heart surgery techniques and devices. “This is really the home of a number of medical device innovations. There is a great medical device community … in Minnesota.”