Scientists' inability to follow the whereabouts of
cells injected into the human body has long been a major
drawback in developing effective medical therapies. Now,
researchers at Johns Hopkins have developed a promising new
technique for noninvasively tracking where living cells go
after they are put into the body. The new technique, which
uses genetically encoded cells producing a natural contrast
that can be viewed using magnetic resonance imaging,
appears much more effective than present methods used to
detect injected biomaterials.
The method, described in the February edition of
Nature Biotechnology, was developed by a team of
researchers from Johns Hopkins' Russell H. Morgan
Department of Radiology and Radiological Science, the
Johns Hopkins
Institute for Cell Engineering and the F.M. Kirby Research
Center for Functional Brain Imaging at the Kennedy
Krieger Institute.
In their study, the researchers used a synthetic gene,
called a reporter gene, that was engineered to have a high
proportion of the amino acid lysine, which is especially
rich in accessible hydrogen atoms. Because MRI detects
energy-produced shifts in hydrogen atoms, when the "new"
gene was introduced into animal cells and then "pelted"
with radio frequency waves from the MRI, it became readily
visible. Using the technique as a proof of principle, the
researchers were able to detect transplanted tumor cells in
animal brains.
"This prototype paves the way for constructing a
family of reporter genes, each with proteins tailored to
have a specific radio frequency response," said MRI
researcher Assaf Gilad, lead author of the study.
Collaborator Mike McMahon, an assistant professor of
radiology at the School of Medicine, said, "The specific
frequencies can be processed to show up as colors in the
MRI image. In a way, it's the MRI equivalent of the green
and red fluorescent proteins found in nature and used by
labs everywhere in the world for multiple labeling of
cells."
The problem with using fluorescent proteins, however,
is that tissue must be removed from the body for
examination under a microscope, which means that the method
isn't suitable for use in patients. "In contrast," said
Jeff Bulte, a professor of radiology, "MRI is noninvasive,
allowing serial imaging of cells and cellular therapies
with a high resolution unmatched by any other clinical
whole-body imaging technique."
Current MRI contrast agents also have several
disadvantages, said Peter van Zijl, founding director of
the Kirby Research Center for Functional Brain Imaging.
"Their concentration becomes lower every time cells divide,
so our ability to see them diminishes. Also, using magnetic
metal allows us to detect only one type of labeled cell at
a time," he said. The new approach is not hampered by these
limitations.
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