Scientists report today that artificial blood vessels made using a person's own skin cells work well in patients receiving kidney dialysis. The new blood vessels mark the first vascular grafts to be derived entirely from a patient's own tissues, which lowers the odds of a harmful immune reaction. Down the road, engineered grafts may also prove useful in treating patients with circulatory problems in their legs and coronary arteries.
About 300,000 people a year in the United States receive regular kidney dialysis, which removes and filters a patient's blood before returning it. To speed the procedure, doctors typically implant a small blood vessel between a vein and an artery in the patient's arm. Blood is then removed and reinserted through an intravenous line inserted into this bypass vessel. When possible, doctors typically harvest a piece of a vein from a patient to make this bypass, called a shunt. But over time, these shunts often fail, forcing doctors to use shunts made with plastics and other synthetic materials that can trigger immune reactions or blood-flow problems downstream.
In hopes of engineering a more natural replacement, researchers led by Todd McAllister of Cytograft Tissue Engineering of Novato, California, came up with a scheme for growing replacement vessels using a patient's own cells. They start by harvesting skin cells known as fibroblasts and growing these in a sheet. They then roll up the sheet and allow the cells to produce an interpenetrating mixture of structural support proteins, known as collagen and elastin.
The trouble with fibroblasts is that they can transform into smooth muscle cells that can eventually clog the vessel. So McAllister's team removed the fibroblasts, leaving behind just the protein scaffold. Then the researchers layered another sheet of fibroblasts on the outside of this scaffold, which is dense enough to prevent the cells from easily migrating to the inside of the engineered vessel. Finally, the team added a layer of the patient's own endothelial cells, which promote smooth blood flow, on the inside of the vessel.
Would the new vessels work? In the current study, McAllister's team implanted them into 10 kidney dialysis patients in Argentina and Poland, all of whom had suffered previous graft failures. Grafts in three patients failed in the first 3 months, a failure rate consistent with a high-risk population, the researchers report today in The Lancet. Two other patients didn't finish the study for reasons unrelated to the grafts. In the remaining five patients, the engineered grafts functioned normally to the study's conclusion, which was between 6 months and 20 months, depending on when the patients enrolled. The ongoing success of the engineered shunts bodes well, McAllister says, because close to half of all plastic shunts fail within 1 year of implantation.
"It is a remarkable accomplishment," says Vladimir Mironov, a tissue engineer at the Medical University of South Carolina in Charleston. Mironov cautions that because it takes up to 9 months to grow the engineered vessels, they will likely be expensive. McAllister agrees but says that the company is currently working to streamline its operations to reduce costs.