Wednesday, June 18, 2008

Magnetic Genes

Genetically engineered cells make their own nanomagnets, providing clear MRI images.

By Lissa Harris

Closer look: This MRI shows a mouse brain that has been injected with transplanted cells that have been genetically engineered, using a gene from a magnetically sensitive bacterium, to produce magnetic nanoparticles. The arrow points to the cluster of magnetically active cells. Credit: Wiley-Liss, a subsidiary of John Wiley & Sons

Using a gene from a magnetically sensitive bacterium, scientists have genetically engineered mammalian cells to produce magnetic nanoparticles. The finding, by a team of Emory University researchers, could give medical researchers a new way to more precisely track cells in the body.

The gene comes from a species of pond-dwelling bacteria that uses it to make tiny particles that function as a kind of biological compass needle. The researchers found that inserting the gene into the DNA of mouse cells caused the cells to produce their own magnetic nanoparticles. When the researchers then injected cells expressing the geneinto the brains of live mice, individual cells could be clearly seen with an MRI as a dark blob surrounded by paler normal tissue.

To track cells in an organism, scientists commonly use genetically engineered fluorescent optical markers such as green fluorescent protein (GFP). By precisely controlling where in the genome the GFP gene is inserted, scientists can "tag" particular proteins that they're interested in, and they can track patterns of gene expression as well as particular kinds of cells.

But unlike an MRI, which can see deep into tissue, fluorescent microscopy is limited to the surface, sometimes making it difficult to get images from within living animals. "The idea of using gene-directed production of MRI contrast is highly desirable," says Xiaoping Hu, a professor of biomedical engineering at Emory and an author of the study. Optical markers, Hu says, "cannot be used to look very deep." The paper by Hu and his colleagues was published in the June issue of Magnetic Resonance in Medicine.

If genetically engineering cells to produce their own magnetic nanoparticles proves successful, this provides a new window through which to view many biological processes as they unfold, from the formation of tumors to the migration of stem cells injected to treat disease. "It's just amazing that they can get a mammalian cell to actually make the material," says Lee Josephson, an associate professor at the Harvard Medical School's Center for Molecular Imaging Research. "I think it's a really meaningful piece of work."

Getting good MRI images at the fine level of resolution needed to see cellular processes unfold has been an elusive goal. One approach, which Josephson helped pioneer, is cell loading--incubating cells with magnetic nanoparticles, then injecting them into the body. But over time, as the magnetically marked cells divide, the signal becomes weaker and is lost. Another cell-labeling technique, just developed in the past few years, is to use a gene that produces ferritin, the molecule that cells employ to store iron. But the form of iron in ferritin is not as easily detected as the nanoparticles used in the Emory study.

While researchers see a lot of potential in the new technique, it has drawbacks. Because of the underlying physics of how an MRI works, the images will never have the fine resolution of surface-level optical microscopy, says Michal Neeman, a professor at the Weizmann Institute of Science, in Israel, who studies molecular imaging using ferritin. And although the study is exciting, she says, "the magnetic properties of the particles need to be studied with more detail."

Still, the fact that a single bacterial gene could get a wide variety of cells to make their own magnets opens up a wide range of possibilities, from new cell imaging techniques to using bacteria as biological factories for producing nanoparticles. "If this technology works well, I think there are massive numbers of applications," says Brian Rutt, a professor at the University of Western Ontario who studies tumor formation.