San Diego, CA, USA. The first lab-grown blood vessels made from donor skin cells uses a new technique for human textiles that promises to cut eventual production costs by half.

The procedure eliminates much of the long lead time needed for making blood vessels from a patient's own cells. The results are a completely human-derived alternative to synthetic blood vessels that resist punctures and infections typical of synthetic materials.


Many people were skeptical when two young California-based researchers set out more than a decade ago to create a completely human-derived alternative to the synthetic blood vessels commonly used in dialysis patients. However, they achieved that that goal and much more since then. "There were a lot of doubts in the field that you could make a blood vessel, which is something that needs to resist pressure constantly, 24-7, without any synthetic materials in it," explains Nicolas L'Heureux, a co-founder and the chief scientific officer of Cytograft Tissue Engineering Inc. in Novalto, California. "They didn't think that was possible at all."



Nicolas L'Heureux is co-founder and the chief scientific officer of Cytograft Tissue Engineering Inc.

L'Heureux presented his team's latest findings at the annual meeting of the American Association of Anatomists (AAA) on 23 April 23 2012.

The meeting was held in conjunction with the Experimental Biology 2012 meeting hosted by the Federation of American Societies for Experimental Biology (FASEB) in Bethesda, MD, USA.But the skeptics were wrong. Cytograft, founded by L'Heureux and Todd McAllister in 2000, developed vessels that L'Heureux says are "completely biological, completely human and living, which is the Cadillac of treatments … and it seems to work really well".

First the team created blood vessels from patients' own skin cells. Then, in June, three dialysis patients had received the world's first lab-grown blood vessels made from skin cells from donors, which eliminates the long lead time needed for making vessels from a patient's own cells. And now a new Cytograft technique for making human textiles is projected to reduce the production cost of these vessels by half.

Laying Foundations For Human Textile

The work remains in the early stages, but an animal trial showed promising results. For one thing, the woven vessel has proved to resist puncture, an important consideration for dialysis and as a step in complex surgical procedures. At this point, the improved approach builds on what already has been proved successful.

• In 2005, the team began extracting fibroblasts from patients' own skin, cultured those cells into thin sheets, rolled up those sheets, cultured them some more so that they would fuse together, and implanted the lab-grown cylindrical vessels.
  
  
• The vessel-growing process was lengthy, at about seven months, but, because the vessels were derived from the patients' own cells, the implants were easily accepted by the patients' bodies, and they held up to the rigors of dialysis, which requires repeated punctures with large-gauge needles.
  
  
• Then the researchers created allogeneic vessels — those grown from donor cells — with the hope that they were laying the foundation for an off-the-shelf stockpile of 100 percent human replacement parts.

"By combining these two methods we could make something that is allogeneic, cheaper to produce, and that you could store forever, meaning that the clinician can pull it off the shelves whenever they want," L'Heureux explains. "If it is frozen and allogeneic, that is kind of the home run."

Those donor-based vessels were implanted into three patients in Poland, and they have performed well with no signs of rejection. From a manufacturing standpoint, that was a big accomplishment since it is very costly to segregate all the patients' cells at all the steps with all the material and all the media and the culturing zones."

Using donor cells dramatically reduces costs to he point where a lab-grown human vessel might cost between US$6,000 to US$10,000 — subject to further reductions with automation and volume. However, the process does not cut down on the manufacturing time because the culturing of the cells so that they fuse together takes many months. So the researchers decided it was time to try out an idea they'd been kicking around for some years: human textiles.

Medical Textile Making

Most medical textiles used today are made of permanent synthetic fibers, such as polyester. They weave synthetic threads to create patches, such as those for blood vessels and can make a large blood-vessel replacement conduit that they use for arterial repair. Or, they can use patches for hernia repair.

Using a different approach, the team deconstructs sheets of cultured cells into threads and uses a variety of medical-textile-making techniques to weave together the blood vessels. "What we are doing here is using a completely biological, completely human — and chemically nonprocessed in any way — fiber from which we can now build all kinds of structures by weaving, knitting, braiding or a combination of techniques," says L'Heureux.

Once the cell sheets are grown, weaving the human textiles into a vessel takes only a couple of days, even with the prototype loom currently used at the Cytograft laboratory. And the threads of cells, while more delicate than synthetic fibers, are strong. "It is not like your grandmother with the little knitting pins," L'Heureux says. "It is much faster than that. Basically, the time it takes for making the threads and assembling them in a blood vessel is negligible compared to the time that it took you to make the sheet."

Aiming For Streamlined and Cost-effective Treatment

L'Heureux notes that, having shown that vessels grown from donor cells are a good, natural alternative to synthetic vessels, it's time to roll out "a treatment that is more streamlined and more cost effective," and this third-generation woven allogeneic blood vessel could be the solution. "We just came to a point where we had proved a lot of what we could do with our blood vessels and it made sense to find a way to make it faster." And this weaving method that makes the vessel out of the same material that is used in the sheet makes it ready in about a third of the time that it took before.

Additionally, the weaving technique actually produces a more robust vessel than one that previously had been cultured in a cylindrical shape. L'Heureux says "There is no seam, which is a problem when you roll something — there's always a flap on the inside and a flap on the outside, and you need to be sure that these flaps are really well fused with the rest, and that takes a long time for the cells to do".

Next Steps

The tissue engineering work remains in the early stages, but an animal trial has already shown promising results. For one thing, the woven vessel has proved to resist puncture, an important consideration for for dialysis. From the beginning, researchers focused primarily on the use of lab-grown blood vessels for dialysis patients because that has been seen as having the largest and most immediate need.

But L'Heureux says they could be used in a variety of other patients. Babies with congenital heart defects, for instance, need replacement vessels that can grow and change. Heart bypass patients today endure the often-painful recovery associated with removing a vessel from one part of the body for implantation elsewhere, and a lab-grown and -woven one could eliminate the need for the first surgery.

Also, human-based replacement vessels are far less susceptible to infection than synthetic ones, L'Heureux emphasizes. "With synthetics, one of the big drawbacks is that they get easily infected. What happens is that the synthetic harbors microbes, and immune cells can't deal with the synthetic. They can't grab it. It's like chasing a dog on an ice rink." Immune cells, meanwhile, can recognize and interact with the lab-grown tissue since it is completely biological.

Despite the doubts about Cytograft's work in the early days, there is a push nowadays for finding natural alternatives to synthetics, in part because of the infection risk, L'Heureux says. "Today, 15 years later, the goal of eliminating synthetic materials from tissue-engineered products has become pretty mainstream."