Engineers Use Blood's Hydrodynamics To Manipulate Stem, Cancer Cells
ScienceDaily (Jan. 23, 2008) — 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 R. King, associate
professor of biomedical engineering at the University of Rochester,
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. "We're finding we can play off the hydrodynamics of moving
blood to isolate and manipulate specific cell populations with great
efficiency."
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, he says.
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 at the University of Rochester,
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—
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—
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. If you use traditional methods to
collect stem cells, centrifuging the rat's blood, even in these drug-
treated rats you might get 3 or 4 percent stem cells—meaning only 3
or 4 percent of the cells you obtain are stem cells."
King points out that centrifugal methods currently produce an overall
higher stem cell yield because they start with far more blood
material, but he believes his microscale device can be scaled up to
significantly larger capacity.
King is even more enthusiastic about his work in reprogramming cells
that pass through his device. As the cell rolls across the adhesive
surface, it can be forced to contact other proteins on the surface.
King says these proteins can be designed to steer a stem cell's
development, forcing it to become a specific type of blood, bone, or
muscle cell.
King hopes someday an implantable device could continuously reprogram
errant neutrophils, but he is already hard at work on a device that
holds the same promise for cancerous cells.
Cancer cells use the same rolling mechanism to travel around the body
and lodge in interstitial tissue, so King has already focused on
isolating the selectins that cancer cells respond to. His lab is
working to create a microscale tube that might attract cancer cells
and use "permanent" receptor-mediated triggering proteins to
reprogram them to self-destruct. With his microscale tube device,
King has already verified that he can control the rolling adhesion of
various types of cancer cells, including leukemias, prostate,
retinoblastoma, and colorectal cancer cells.
"One of our ultimate goals is to develop an implantable device that
will selectively remove metastatic cells from the blood," says
King. "Those cells can predate detectable tumors by years, so we
might catch them before they become dangerous."
This research was funded by the New York State Foundation for
Science, Technology and Innovation, and by CellTraffix, a company in
which King holds a financial interest. Other authors on the British
Journal of Haematology paper include University of Rochester
postdoctoral students Joel C. Wojciechowski and Srinivas D.
Narasipura, doctoral student Nichola Charles, Deanne Mickelsen,
laboratory technician, and Martha L. Blair, professor in the
Department of Pharmacology and Physiology.
Adapted from materials provided by University of Rochester.
Need to cite this story in your essay, paper, or report? Use one of
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MLA University of Rochester (2008, January 23). Engineers Use
Blood's Hydrodynamics To Manipulate Stem, Cancer Cells. ScienceDaily.
Retrieved January 23, 2008, from http://www.scienced
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http://www.CNSfoundation.org/
Cord Blood Registry
http://www.CordBlood.com/at.cgi?a=150123
The CNS Healing Group
http://groups.yahoo.com/group/CNS_Healing
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