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How to track a stem cell
Posted by Andrea Gawrylewski
[Entry posted at 1st May 2008 03:32 PM GMT]
Before therapies using human embryonic stem cells can be approved by the
Food and Drug Administration, researchers will have to answer one key
question: where do the cells go when they are injected into the patient?
During an FDA meeting earlier this month on the safety of embryonic stem
cell therapies, the agency grappled with the issues of tracking stem cells
in vivo. Regardless of whether stem cells need to target a specific
location, such as the eye, or circulate the body, researchers need
standardized tools to watch where the cells go and how they differentiate.
But some experts wonder what the priorities should be in developing stem
cell therapies. At the FDA meeting, Kenneth Chien, from Harvard Medical
School, asked whether new stem cell tracking technologies that are so far
away are worth investing time and money in.
I called up Jeffrey Bulte from Johns Hopkins University, who gave a
presentation on the subject at the FDA meeting, and asked him to give a run
down of tools his group is developing. First, a clinically approved
radiolabeling agent for immune response and inflammation, called Indium
Oxine, can be used to track embryonic stem cells. In 2005, Bulte and
colleagues used Indium Oxine to watch canine bone marrow-derived mesenchymal
stem cells disperse to other organs after being injected into the blood.
Using a specialized CT scanner, the researchers could see "hot spots" of the
cells in the heart, liver, and kidney, Bulte told The Scientist.
Bulte and other researchers are also developing reporter genes that are
inserted into a stem cell's genome. These genes contain luciferase, the
enzyme that makes fireflies glow; it lights up in living cells, and
researchers can image the marker in small animals. But the much larger human
body absorbs the light, so the technique won't work in the clinic. Also,
reporter genes genetically alter cells, so there is a risk of side
effects -- most importantly, altered cells are no longer stem cells and may
behave differently than the population of stem cells as a whole. "The Holy
Grail would be an MRI reporter gene" that provides MRI contrast in stem
cells, Bulte said in his talk at the FDA meeting.
Bulte's team is also developing capsules for tracking cells. "We encapsulate
cells, put them in protective housing, label these capsules, and inject
them," he said. "And using MRI we can see where they go." This technique
allows the cell material to be protected and also released in a controlled
way.
But MRI isn't sensitive enough to track cells efficiently with these
techniques. In collaboration with Philips Research in Hamburg, Bulte is
developing a new imaging tool called magnetic particle imaging (MPI), which
flips the magnetic field around a tissue sample back and forth and captures
images as magnetically-treated cells give off a frequency. MPI is more
sensitive to cell numbers than MRI and does not pick up the surrounding
tissue, as does MRI, Butte said, but the technology may not be implemented
for many years to come. He plans to present the concept and initial results
at the annual meeting of the International Society of Magnetic Resonance in
Toronto next week.
Rayilyn Brown
Director, AZNPF
National Parkinson's Foundation
rbrown@xxxxxxxxx
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