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.
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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.
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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.