Researchers Use Magnetism to Target Cells to Animal Arteries
- Magnetically Guided Nanoparticles May Deliver Treatments to
Human Organs -
PHILADELPHIA, Jan. 7 /PRNewswire-
used magnetic fields and tiny iron-bearing particles to drive healthy
cells to targeted sites in blood vessels. The research, done in
animals, may lead to a new method of delivering cells and genes to
repair injured or diseased organs in people.
The study team, led by Robert J. Levy, M.D., the William J.
Rashkind Chair of Pediatric Cardiology at The Children's Hospital of
Philadelphia, loaded endothelial cells, flat cells that line the
inside of blood vessels, with nanoparticles, tiny spheres nanometers
in diameter. The nanoparticles contained iron oxide.
Using an external, uniform magnetic field, Levy's team directed
the cells into steel stents, small metal scaffolds that had been
inserted into the carotid arteries of rats. The uniform magnetic
field created "magnetic gradients," local regions of high magnetic
force that magnetized both the nanoparticles and the stents, thus
increasing the attraction between the particles and their target.
The study appears in the Proceedings of the National Academy of
Sciences, published online on Jan. 7. Dr. Levy's group from Children's
Hospital collaborated with engineers from Drexel University and Duke
University.
"This is a novel strategy for delivering cells to targets in the
body," said Levy, who added that previous researchers have pursued
other, less successful approaches to introduce endothelial cells to
diseased blood vessels, in the developing medical field of cell
therapy.
Levy's team created nanoparticles, approximately 290 nanometers
across, made of the biodegradable polymer, polylactic acid, and
impregnated with iron oxide. (A nanometer is a millionth of a
millimeter; in comparison to these nanoparticles, red blood cells are
ten to 100 times larger.)
The researchers loaded the nanoparticles into endothelial cells,
which had been genetically modified to produce a specific color that
could be detected by an imaging system while the animals were alive.
After introducing stainless steel stents into rats' carotid arteries,
Levy's team used magnetic fields to steer the cells into the stents.
Patients with heart disease commonly receive metal stents in
partially
blocked blood vessels to improve blood flow, both by widening the
vessels
and delivering drugs. However, many stents fail over time as smooth
muscle
cells accumulate excessively on their surfaces and create new
blockages.
One goal of cell therapy is to introduce new endothelial cells to
recoat
stents with a smooth surface.
Furthermore, Levy adds, while drug-releasing stents currently
provide benefits in treating diseased coronary arteries, they have
proved far less effective in treating peripheral vascular disease,
such as that occurring in patients with diabetes. In such cases,
severe problems in blood circulation may force doctors to amputate a
leg. In upcoming animal studies, Levy's team will use their delivery
approach to deliver magnetic nanoparticles to peripheral arteries.
Future studies, Levy added, also will use cells derived from the
animal itself, to avoid potential rejection problems that may occur
with unmatched cells. The current study used unmatched cells,
delivering bovine cells to rat arteries, but only over a 48-hour
period, too brief for rejection to occur.
The current study builds on research published earlier this year
by
Levy and collaborators, in which they used magnetic fields and
nanoparticles to deliver DNA to arterial muscle cells in culture. That
research focused on a delivery system for gene therapy, while the
current
study represents cell therapy. Levy suggests future applications may
combine both therapies, using endothelial cells to deliver beneficial
genes
to damaged arteries.
The delivery system, says Levy, might also be applied to other
sites
where physicians implant steel stents to deliver medication, such as
the
esophagus, bile ducts and lungs. Another potential use might be in
orthopedic procedures, in which surgeons implant steel nails to
stabilize
fractured bones, or use steel screws to correct spinal abnormalities.
In
such cases, magnetized nanoparticles might deliver bone stem cells to
strengthen bony structures.
"Magnetic fields produced by ordinary MRI machines could suffice
to
deliver cells to targets where they could promote healing, since MRI
uses
uniform fields, which are key to our targeting strategy," added
Levy. "This
method could become a powerful medical tool."
Financial support for the study came from the National Institutes
of
Health, the Nanotechnology Institute, and both the William J. Rashkind
Endowment and Erin's Fund of The Children's Hospital of Philadelphia.
Dr. Levy's co-authors were Ilia Fishbein, M.D., Michael Chorny,
Ph.D., Ivan S. Alferiev, Ph.D., and Darryl Williams, of Children's
Hospital; Boris Polyak, M.D., and Gary Friedman, Ph.D., of Drexel
University; and Ben Yellen,
Ph.D., of Duke University.
About The Children's Hospital of Philadelphia: The Children's
Hospital
of Philadelphia was founded in 1855 as the nation's first pediatric
hospital. Through its long-standing commitment to providing
exceptional
patient care, training new generations of pediatric healthcare
professionals and pioneering major research initiatives, Children's
Hospital has fostered many discoveries that have benefited children
worldwide. Its pediatric research program is among the largest in the
country, ranking third in National Institutes of Health funding. In
addition, its unique family-centered care and public service programs
have brought the 430-bed hospital recognition as a leading advocate
for children and adolescents. For more information, visit
http://www.chop.
CONTACT: John Ascenzi of the Children's Hospital of Philadelphia,
+1-267-426-6055, Ascenzi@email.
SOURCE The Children's Hospital of Philadelphia
http://www.prnewswi
ACCT=159681&
2008/0004732188&
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StemCells subscribers may also be interested in these sites:
Children's Neurobiological Solutions
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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