February 4, 2008
Engineers design a cell retriever and reprogrammer
jonathan.sherwood@rochester.edu
A tiny, implantable device has pulled adult stem cells
out of a living rat with a far greater purity than any present technique.
The test of the device designed by Michael King,
associate professor of biomedical engineering, will be reported in the
March 3 issue of the British Journal of Haematology.
“It’s the kind of research that, before we
tried it, we never would have expected such a remarkable result straight
out of the gate,” says King.
King is at the forefront of a new field, manipulating
stem cells, white blood cells, and even cancer cells by exploiting the
mechanics of the cells’ movement with such precision that he is
having success capturing and even reprogramming several cell types as they
pass through the device.
A chance encounter between an engineer and a
hematology clinician gave rise to the field in 2002. King was studying how
certain white blood cells, called neutrophils, know how to migrate to a
point of infection. He observed how, near an injury site, the walls of the
nearby blood vessels expressed an adhesive protein called a selectin, and
if passing neutrophils brushed against these selectins, they stuck to the
vessel wall.
But the cells did not remain stuck—they rolled.
With a precise balance between the adhesion of the selectins and the forces
of the flowing bloodstream, the cells could move much more slowly as they
approached the infection site. With that slowed pace, the cell can look for
a second signal on the vessel wall that tells the cell to exit the vessel
by squeezing between cells in the wall and moving directly to the site of
infection.
One reason the system is so effective is that only the
neutrophils respond to those selectins, so only neutrophils slow down in
the blood.
King was working out the physical dynamics of this
neutrophil rolling in his office one day when Jane Liesveld, a hematology
clinician doing work on bone marrow stem cells, walked by and noticed a
poster of King’s work in the hallway outside his office.
“She dropped in and said, ‘I have a pretty
plentiful source of primary stem cells from patients. Can you think of any
biophysical research to do with that?’” says King. “The
stem cell angle just fell from the sky.”
As King worked with Liesveld, he found that the basic
rolling mechanism was the foundation of a number of other processes,
including stem cell transplantation—a natural phenomenon where stem
cells move in and out of bone tissue via the blood. In 2004, he found that
he could coat a material with specific adhesive selectins and capture
living stem cells. This collaboration resulted in two human stem cell
papers published just within the last month: in Biotechnology Progress (Charles
et al., 2007) and Clinical Chemistry (Narasipura et al., 2007).
In the new British
Journal of Haematology paper, King and
colleagues show they can take the process a step further by implanting
the device in a living rat with the selectin coating remaining active for
1-2 hours. When the tube was removed, King found he’d indeed captured
cells straight out of the bloodstream, including
contaminants—non-stem cells—as expected. What he didn’t
expect was how many of the cells were viable stem cells.
“I was astounded,” says King. “More
than 25 percent of the sample was stem cells. It’s amazing because
even when you use drugs to increase the number of free stem cells in the
blood, they still only make up less than 1 percent of all cells.”
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