A technique that combines gene therapy and magnets could someday provide a new tool for treating cardiovascular disease, which puts millions of lives at risk every year. Researchers have produced cells that carry magnetic nanoparticles linked to a therapeutic gene. With an external magnet to direct the cells, the researchers used them to repair damaged arteries in mice (ACS Nano 2015, DOI:10.1021/acsnano.5b04996).
Clogged arteries can cause heart attack or stroke. Blockages happen when the smooth single-cell lining, or endothelium, of an artery gets damaged from aging or disorders like high cholesterol, allowing plaque to start growing on the walls. Endothelial cells also produce nitric oxide, essential for dilating blood vessels so blood can flow. Areas without endothelial cells are constricted and have less blood flow, allowing further plaque deposits. Doctors can remove the plaque or open blocked vessels surgically, but even less-invasive procedures like angioplasty scrape off the endothelial cell lining, allowing plaque to form again.
To restore the epithelial lining, researchers have tried infusing the damaged site with endothelial cells, cell growth proteins, or genes that code for enzymes that synthesize nitric oxide. But when the cells and molecules are injected, blood flow flushes these agents away. Implanted stents provide another delivery option, but that requires a surgical procedure.
Daniela Wenzel, a physiology researcher at the University of Bonn, and her colleagues looked for a new way to direct injected cells to the right place and keep them there. First they packaged genes coding for a green fluorescent protein and a nitric oxide-synthesizing enzyme within a viral vector, commonly used to deliver genetic material into cells. They linked the vectors to magnetic, silica-iron oxide nanoparticles, and loaded the vector-nanoparticle combo into endothelial cells. “The cells become magnetic so they can be positioned by external magnets,” she says.
The researchers then injected engineered cells into the carotid arteries of mice where the endothelial cells within those vessels had been removed. In half of the animals, they placed a magnet over the treatment site for 30 minutes. Two days later, the arteries of animals exposed to magnets showed green fluorescing cells attached to their inner surfaces, covering at least half of the circumference. In the other animals, blood flow had swept the introduced cells out of the arteries and deposited them in the brain.
Isometric force measurements on removed carotid arteries showed that the magnetically treated arteries were able to contract and expand, while the untreated arteries could not, showing that the grafted cells were doing their job producing nitric oxide.
The team’s first goal is to improve healing after surgery, Wenzel says. But eventually the technique could be used preventatively to reduce plaque buildup or for those at risk of coronary heart disease. But before this technique could move to the clinic, the researchers will need to test it in larger animals and design better, stronger magnet assemblies for use in humans.
“Slow and often incomplete recovery of functional endothelium is an important problem associated with angioplasty,” says Michael Chorny, a cardiology researcher at the Children’s Hospital of Philadelphia. This new study shows “an elegant combination of cell and gene therapy.”