Stents are expandable stainless-steel scaffolds commonly used to prop open clogged arteries. But inserting a stent can damage an artery’s inner lining, and stented arteries may reclose after several months, causing blood clots and possibly heart attacks. Now researchers at the Children’s Hospital of Philadelphia have devised a way to use tiny iron-bearing nanoparticles and a magnetic field to direct cells with therapeutic properties to the sites of steel stents. The cells could help repair arterial damage and prevent clotting, among other things.
“Stents have been known to induce severe trauma,” says Robert Levy, chair of pediatric cardiology at the Children’s Hospital of Philadelphia. “Repairing blood vessels with cell therapy is a very important concept that can be realized with magnetic targeting.”
Levy and his colleagues engineered nanoparticles, or tiny spheres, of polylactic acid, a biodegradable polymer used in sutures and other medical applications. The team then loaded each nanoparticle with a small dose of magnetically responsive iron oxide and inserted it into a bovine endothelial cell–a cell found in a blood vessel’s inner lining. The bovine cells were genetically altered to express a fluorescent marker, making them easily detectable.
Next, the researchers surgically implanted small metal stents in the carotid arteries of live rats. They injected the rats with a solution of treated endothelial cells and created a steady magnetic field around each rat using two large, external electromagnetic coils. Levy says that the magnetic field he and his colleagues applied was less than a tenth of the strength of the fields generated by conventional MRI machines. After 48 hours, the team created images of the rat using bioluminescence imaging.
The researchers found that the magnetic field caused the cells to migrate to the metal stents under two scenarios: when cells were injected directly into the carotid artery, near the stent location, and when they were injected farther away, in the aortic arch, whence they could have branched out to all areas of the body. In tests that didn’t use a magnetic field, the cells migrated throughout the body with little direction.
Magnetically directing cells, particularly endothelial cells, to the sites of metal stents may have a significant therapeutic effect, says Levy. During surgical implantation, stents tend to scrape off endothelial cells, whose normal functions include helping prevent blood clotting. Endothelial cells are also barriers to inflammatory cells. While inflammatory cells normally flock to an injury to help repair it, in the absence of endothelial cells, they build up excessively, creating arterial blockage. In recent years, stents have been engineered to release anticlotting drugs to prevent arteries from reclosing. But such drug-releasing stents have problems of their own, including preventing endothelial cells from regenerating.