A FRAGMENT of HIV has been used to create minuscule magnetic beacons for
tracking living cells as they move through the body. The technique could be a
crucial tool for developing and improving stem cell therapies.
The cores of the beacons are specks of easily magnetised iron oxide just 45
nanometres across. These are coated with a glucose polymer called dextran to
make them compatible with living tissue. There have been attempts to use such
nanoparticles to track cells before, but researchers found them ineffective
because most cells would not take them up.
But this month, scientists led by Ralph Weissleder at a Harvard Medical
School hospital in Charlestown, Massachusetts, revealed a solution. The group
adds a snippet of a HIV protein known as “Tat” to the particles. Tat helps to
get HIV into cells unnoticed and confers the same ability on the nanoparticles,
allowing them to invade a cell so that it can be tracked.
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Using the nanoparticles, the researchers have already tracked cells in mice
and rats. They tag cells by placing them in a solution of the nanoparticles,
many of which end up in each cell. “They act like one big magnet,” says
Weissleder.
These magnets can be tracked using magnetic resonance imaging. In the first
experiments, the particles could only be followed for about seven days before
they disintegrated. But recent improvements in the coating have bumped up their
lifespan to three weeks, says Weissleder.
The team has tagged both haematopoietic progenitor cells, which form blood
cells, and neural progenitor cells. Progenitor cells are descended from stem
cells—which have the potential to develop into any tissue—and are
the earliest level of specialisation.
Blood stem cells are already given to patients with damaged immune systems.
They lodge in bone marrow and produce new blood and immune cells
(New Scientist, 14 August 1999, p 6).
Exactly how the cells home in on bone
marrow is not yet understood, but researchers know that only a small percentage
make it.
The new beacons offer the first chance to follow the homing of haematopoietic
cells in a living animal and gauge how many cells make it to the marrow. “That
would be quite useful to be able to follow what happens,” says Loren Field, a
biologist at Indiana University in Indianapolis, who works with stem cells.
Because the beacons are magnetic, researchers can retrieve the cells after an
experiment. That will give them the chance to analyse cells that do make it to
bone marrow and find ways to increase the number that reach the target.
Researchers also hope to find better ways of getting neural and other stem cells
to damaged areas, where they can generate new cells.
Weissleder says the group is aiming to carry out trials in humans within the
next three years.
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Source:
Nature Biotechnology (vol 18, p 410)