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ATLANTA—Emory University and Georgia Tech have joined forces on research that embeds microscopic magnets inside of stem cells in order to steer the cells to specific sites within the body. This approach is being explored as a new treatment option for the correction of vascular damage.
This work was the result of collaboration between the laboratories of Dr. W. Robert Taylor, professor of medicine and biomedical engineering and director of the Division of Cardiology at Emory University School of Medicine, and Dr. Gang Bao, professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University.
This approach combines nanoparticles of magnetized iron oxide with mesenchymal stem cells, which are then injected intravenously and can be attracted to desired locations of the body by using magnets. Mesenchymal stem cells can be harvested from adult tissues, such as fat or bone marrow, and can differentiate into bone, fat and cartilage cells. They secrete a variety of anti-inflammatory factors, and one of their main benefits is that they produce angiogenic factors, says Taylor. While the cells themselves don't play a role in the development of new blood vessels, "they generate the growth factors that encourage or enhance local growth of blood vessels."
The magnetized nanoparticles are loaded into the stem cells by using a magnetic field to push them into the cells, and are coated with a polyethylene glycol coating that protects the cells from damage.
"We were able to load the cells with a lot of these nanoparticles, and we showed clearly that the cells were not harmed," said Taylor in a press release. "The coating is unique and thus there was no change in viability—and, perhaps even more importantly, we didn't see any change in the characteristics of the stem cells, such as their capacity to differentiate. This was essentially a proof-of-principle experiment. Ultimately, we would target these to a particular limb, an abnormal blood vessel or even the heart."
After entering the cells, the nanoparticles seem to stick within the cells' lysosomes, and remain for at least a week. No leakage was detected, and by measuring the iron content of the cells after they were loaded up, they found that each cell absorbed approximately 1.5 million particles.
When testing this in mouse models, the team was able to use a bar-shaped rare earth magnet to attract the injected stem cells to the tail when applied to a section of the tail near where the cells were being injected. Ordinarily, most of the stem cells would end up in the liver or the lungs. The researchers were also able to track the progress of the cells by labeling them with a fluorescent dye. It was calculated that the bar magnet increased the presence of the cells in the tail by six times.
Taylor notes that while this approach could be used with a variety of other cell types, mesenchymal stem cells were more relevant to some of their other research projects, represented a more stable cell line and also allow autologous use.
"For us, our interests are in vascular biology, and we want to be able to localize them to a particular vascular bed where you need to grow some new blood vessels or you need to have vasculogenesis occur, or collateral vessels grow," Taylor explains.
He adds that this approach could have potential in treating stroke or in the myocardium as well, noting that it could be useful "any place where you needed to repair the vascular supply."
Taylor and his colleagues are now working with these nanoparticle-loaded stem cells to direct the mesenchymal stem cells to specific sites in ischemic limbs in animal models. Human patients with ischemic limbs have no real therapeutic options beyond amputation, says Taylor.
The paper, "Magnetic targeting of human mesenchymal stem cells with internalized superparamagnetic iron oxide nanoparticles," was published online in Small. This research was supported by the National Heart Lung and Blood Institute's Program of Excellence in Nanotechnology.