Using tiny rust-containing spheres to tag cells, scientists from Johns Hopkins and elsewhere have successfully used magnetic resonance imaging to track stem cells implanted into a living animal.
The team said the neuronal stem cells take up and hold onto the spheres, which contain a compound of iron and oxygen. The iron-laden cells create a magnetic black hole, which is easily spotted by magnetic resonance imaging (MRI) they report.
‘Until now, tissue had to be removed from an animal to see where stem cells were going, so this gives us an important tool,’ said author of the research Jeff Bulte, Ph.D., associate professor of radiology at the Johns Hopkins School of Medicine. ‘Tracking stem cells non-invasively will likely be required as research advances, although human studies are still some time away.’
Scientists at the University of Wisconsin School of Veterinary Medicine mixed the magnetic spheres, made by Trevor Douglas at Temple University, with stem cells that make the white matter, or neuronal covering, of the brain.
Then they injected the iron-laden cells into the brains of rats that lack that covering. Using MRI scanners at the US National Institutes of Health, Bulte watched the cells travel away from the injection site.
The rusty spheres, known as magnetic dendrimers, represent an important improvement over other magnetic tags, Bulte said. And even though the amount of iron used to label the cells is tiny compared to the total amount of iron in the body, the labelled cells stand out from other cells because of their magnet properties.
‘During scanning, these labelled cells disturb the magnetic field created by the MRI machine, causing water molecules that pass by to get ‘out of phase,” he explains. ‘When this happens, the imaging scanner loses the signal, and the area looks black on the image.’
Other researchers have used dendrimers containing gadolinium, which is also useful as a contrast medium for MRI, but which is toxic if it stays in the body for a prolonged time. But animal cells have a process to deal with iron and a storage mechanism for the metal, making the iron-based dendrimers inherently safer, said Bulte.
He added that while it was not easy to develop the way to make magnetic dendrimers, it is easy to label cells with them. In essence, the dendrimer and the cell do that work themselves. Dendrimers stick to cells because they are charged. Cells then suck them inside and lock them away in the cellular holding spot called an endosome.
Other magnetic tags have used antibodies or other molecules that recognise and bind to certain features on cells, said Bulte. Unlike those tags, the magnetic dendrimers are universal; the scientists showed that different cell types will take in dendrimers by mixing the spheres and the cells together, without affecting the cells’ behaviour.