This work was the result of collaboration between thelaboratories of Dr. W. Robert Taylor, professor of medicine andbiomedical engineering and director of the Division of Cardiology at EmoryUniversity School of Medicine, and Dr. Gang Bao, professor in the Wallace H.Coulter Department of Biomedical Engineering at Georgia Tech and EmoryUniversity.
This approach combines nanoparticles of magnetized ironoxide with mesenchymal stem cells, which are then injected intravenously andcan be attracted to desired locations of the body by using magnets. Mesenchymalstem cells can be harvested from adult tissues, such as fat or bone marrow, andcan differentiate into bone, fat and cartilage cells. They secrete a variety ofanti-inflammatory factors, and one of their main benefits is that they produceangiogenic factors, says Taylor. While the cells themselves don't play a rolein the development of new blood vessels, "they generate the growth factors thatencourage or enhance local growth of blood vessels."
The magnetized nanoparticles are loaded into the stem cellsby using a magnetic field to push them into the cells, and are coated with apolyethylene glycol coating that protects the cells from damage.
"We were able to load the cells with a lot of thesenanoparticles, and we showed clearly that the cells were not harmed," saidTaylor in a press release. "The coating is unique and thus there was no changein viability—and, perhaps even more importantly, we didn't see any change inthe characteristics of the stem cells, such as their capacity to differentiate.This was essentially a proof-of-principle experiment. Ultimately, we wouldtarget these to a particular limb, an abnormal blood vessel or even the heart."
After entering the cells, the nanoparticles seem to stickwithin the cells' lysosomes, and remain for at least a week. No leakage wasdetected, and by measuring the iron content of the cells after they were loadedup, they found that each cell absorbed approximately 1.5 million particles.
When testing this in mouse models, the team was able to usea bar-shaped rare earth magnet to attract the injected stem cells to the tailwhen 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. Theresearchers were also able to track the progress of the cells by labeling themwith a fluorescent dye. It was calculated that the bar magnet increased thepresence of the cells in the tail by six times.
Taylor notes that while this approach could be used with avariety of other cell types, mesenchymal stem cells were more relevant to someof their other research projects, represented a more stable cell line and alsoallow autologous use.
"For us, our interests are in vascular biology, and we wantto be able to localize them to a particular vascular bed where you need to growsome new blood vessels or you need to have vasculogenesis occur, or collateralvessels grow," Taylor explains.
He adds that this approach could have potential in treatingstroke or in the myocardium as well, noting that it could be useful "any placewhere you needed to repair the vascular supply."
Taylor and his colleagues are now working with thesenanoparticle-loaded stem cells to direct the mesenchymal stem cells to specificsites in ischemic limbs in animal models. Human patients with ischemic limbshave no real therapeutic options beyond amputation, says Taylor.
The paper, "Magnetic targeting of human mesenchymal stemcells with internalized superparamagnetic iron oxide nanoparticles," waspublished online in Small. Thisresearch was supported by the National Heart Lung and Blood Institute's Programof Excellence in Nanotechnology.