Researchers Make Test-Tube Blood Vessels

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Oct. 2, 2000 (Atlanta) -- Each year, thousands of people with vascular disease are unable to undergo life-saving, symptom-relieving bypass surgery because they have exhausted their supply of usable veins and arteries. Now, researchers have developed a way to create fully functioning blood vessels in a test tube. Although their success so far has been limited to use in research animals, these bioengineered vessels could eventually provide a replenishable source of graft material for human patients.

"CABG, or coronary artery bypass grafting, is ... the most common [heart-surgery] procedure in the U.S. today, with more than 600,000 grafts placed annually. But grafts last only about 10 years," researcher Laura E. Niklason, MD, PhD, an assistant professor of anesthesia and biomedical engineering at Duke University in Durham, N.C., told attendees of a scientific conference held here this week.

During bypass grafting procedures, veins taken from patients' legs are used to literally bypass the vessels that are blocked, to keep the affected areas supplied with blood.

Over the past two years, Niklason's team has developed a system that, in about eight weeks, produces functioning arteries from just a few cells. First, the cells are taken from the blood vessel of a healthy cow or pig. The researchers scatter these cells onto a biodegradable "scaffolding" in a small glass container filled with a "nutrient medium of vitamins, minerals, and proteins that feed the growing blood vessel," she says.

The key to producing vessels that look right and function properly, Niklason says, is a small pump. She says this pump, attached to the glass container, "provides a flow of liquid that mimics the action of the pumping heart on these vessels, so they're stretched while they're growing." The system can be fine-tuned to "produce the optimal engineered vessel," which is just as strong as natural veins and arteries, she says. Even to the trained eye, she says, they are very hard to tell from natural vessels.

The resulting vessels are then grafted into the animal that donated the cells. With no foreign tissue, there is no chance of rejection. So far, healthy pigs implanted with these grafts have done quite well, says Niklason, and at up to four months after the procedure, angiograms -- in which dye is injected into the vessels to let researchers look at them -- show clear, functioning vessels.


But, she tells WebMD, there has not been much success translating the work to humans: "We can apply the same techniques to human cells and get them to grow, but they don't grow well enough to form vessels." The stumbling block "is a cellular age problem," she says. "The cell doubling rate -- how quickly [the cells] multiply -- is very low in elderly humans." While healthy pig cells quickly multiply in the nutrient medium, harvested human cells "have about 10 doublings before they conk out and die," she says.

The team is working on "optimizing the biochemical environment to get the human cells to grow," but wimpy cells are not the only obstacle, admits Niklason.

Recent discoveries have changed the way scientists look at atherosclerosis, or clogging of the arteries. Rather than being a problem with the blood vessels per se, it is now thought to involve inflammation, genetics, and any number of other as-yet-undetermined factors. A major question, then, is how well engineered vessels will fare when they are made up of cells that have this original problem and then put back into people.

"All of the experiments we've done have been on healthy, non-atherosclerotic animals," says Niklason. "It's really an open question how human vessels will do if we grow them from cells taken from atherosclerotic [vessels]."

Niklason is confident that eventually researchers will devise a way to make bioengineered vessels a reality for human patients. "We'll solve it," she says. "In 4 1/2 years, we've taken the project from absolute ground zero to making it work in animals. ... There's no fundamental reason why this isn't going to work. I think it's just a matter of time."

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