Engineered blood vessels prove durable and clot resistant

American Heart Association meeting report

Researchers have built mechanically sound blood vessels out of tissue from human skin cells, according to a study reported today at the American Heart Association’s Scientific Sessions 2002. The technique involves tissue engineering, an emerging science that takes cells from the body, manipulates them in the laboratory to create functional tissue, and puts the new tissue back into the patient.

The goal is to produce healthy, functioning blood vessels built exclusively from a person’s own cells, so the body’s immune system won’t reject the new tissue. Such vessels would be important in heart and leg bypass operations and for vessels called arteriovenous shunts used for dialysis patients.

The scientists reported that tissue-engineered blood vessels didn’t burst or develop blood clots in laboratory tests and short-term animal experiments.

“The study’s most important findings were: First, the technology works from a commercial perspective, meaning we can build mechanically sound vessels for a wide array of patients using the exact same protocol,” says Todd McAllister, Ph.D., president and chief executive officer of Cytograft Tissue Engineering in Novato, Calif., which developed the vessel-building technique.

“Second, we demonstrated that thrombogenesis (the formation of blood clots) does not appear to be a problem in the short term – up to 14 days. Short-term blood clots are the biggest challenge facing most synthetic materials, whether they are used for blood vessels, new heart valves, or other vascular prostheses. We expect to begin this research in humans within 18 months.”

In the study reported today, researchers took fibroblast cells from 11 patients (ages 54 to 84) with advanced cardiovascular disease who had coronary artery bypass operations at Stanford University. Fibroblasts form the outer wall of blood vessels. The researchers used endothelial cells from animals to make the inner lining of the vessels.

Typically, tissue engineering involves growing cells on a synthetic scaffold to create a specific shape, such as a piece of bone for use in facial reconstruction surgery. These scaffolds have traditionally been necessary to provide mechanical strength to the new tissue.

However, Cytograft’s chief scientific officer Nicolas L’Heureux, Ph.D., has developed a different approach called sheet-based tissue engineering.

“We can build a tissue that is only a few hundred microns thick, the diameter of several human hairs, that is robust enough that we don’t need synthetic materials or scaffolding to support it,” L’Heureux says. The cell sheets are removed from the dish and wrapped around a temporary stainless steel cylinder 4 millimeters (0.15 inch) in diameter. The vessel then goes through a maturation phase where the separate layers fuse into a homogeneous tissue.

After removing the tissue from the steel cylinder, endothelial cells are seeded to the inside to create the inner lining of the blood vessel. Finally, the vessels are exposed to increasing rates of fluid flow and pressure to precondition them for implantation.

The engineered vessels were implanted as a femoral (leg) artery graft in study animals. The vessels were then removed at three, seven and 14 days after implantation. All but two of the vessels survived past day three and seemed mechanically stable without forming blood clots.

One question they had going into this study is whether the same chemicals and techniques that could successfully engineer tissue cells from one human into a new blood vessel would also work on cells from other humans.

“It was quite conceivable that differences from patient to patient would be so significant that the same recipe for making blood vessels could not be used in all cases,” McAllister says. “We had no idea whether we could do this across a wide range of age- and risk-matched patients.”

With early evidence showing the vessels’ reliability and clot resistance, researchers plan to implant tissue-engineered blood vessels in humans in 12 to 18 months, he says. The first patients will be those with peripheral vascular disease, the severe blockage of a leg artery that can lead to amputation.

Co-authors are Mark Koransky, M.D.; Nathalie Dusserre, Ph.D.; Gerhardt Konig, B.S.; and Robert Robbins, M.D. Abstract 1864