http://www.hopkinsmedicine.org/press/2001/DECEMBER/011214.htm
December 14, 2001
Using tiny rust-containing spheres
to tag cells, scientists from Johns Hopkins and elsewhere have successfully
used magnetic resonance imaging to track stem cells implanted into a living
animal, believed to be a first.
In the December issue of the journal
Nature Biotechnology, the team said the neuronal stem cells take up and
hold onto the spheres, which contain a compound of iron and oxygen. The
iron-laden cells create a magnetic black hole easily spotted by magnetic
resonance imaging, or MRI, they report.
"Until now, tissue had to be removed
from an animal to see where stem cells were going, so this gives us an
important tool," says author Jeff Bulte, Ph.D., associate professor of
radiology at the Johns Hopkins School of Medicine. "Tracking stem cells
non-invasively will likely be required as research advances, although human
studies are still some time away."
Scientists at the University of Wisconsin
School of Veterinary Medicine mixed the magnetic spheres, made by Trevor
Douglas at Temple University, with stem cells that make the white matter,
or neuronal covering, of the brain. Then they injected the iron-laden cells
into the brains of rats that lack that covering. Using MRI scanners at
the National Institutes of Health, Bulte watched the cells travel away
from the injection site. The research was funded by the National Science
Foundation, the Oscar Rennebohm Foundation and the Keck Foundation.
The rusty spheres, known as magnetic
dendrimers, represent an important improvement over other magnetic tags,
Bulte says. And even though the amount of iron used to label the cells
is tiny compared to the total amount of iron in the body, the labeled cells
stand out from other cells, magnetically speaking.
"During scanning, these labeled cells
disturb the magnetic field created by the MRI machine, causing water molecules
that pass by to get 'out of phase,'" he explains. "When this happens, the
imaging scanner loses the signal, and the area looks black on the image."
Other researchers have used dendrimers
containing gadolinium, which is also useful as a contrast medium for MRI,
but which is toxic if it stays in the body for a prolonged time. But animal
cells have a process to deal with iron and a storage mechanism for the
metal, making the iron-based dendrimers inherently safer, says Bulte. For
instance, iron is a key part of the transporter for oxygen and carbon monoxide
found in red blood cells.
He adds that while it was not easy
to develop the way to make magnetic dendrimers, it is easy to label cells
with them. In essence, the dendrimer and the cell do that work themselves.
Dendrimers stick to cells because they are charged -- kind of like static
electricity. Cells then suck them inside and lock them away in the cellular
equivalent of a garbage can -- a tiny holding spot called an endosome.
Other magnetic tags have used antibodies
or other molecules that recognize and bind to certain features on cells,
says Bulte. Unlike those tags, the magnetic dendrimers are universal; the
scientists showed that different cell types will take in dendrimers just
by mixing the spheres and the cells together, without affecting the cells'
behavior.
Bulte's research with magnetic dendrimers
is aligned with the Johns Hopkins Institute of Cell Engineering, created
in early 2001 to advance research into the biology and potential application
of pluripotent stem cells (primitive cells that become any type of cell
in the body) and multipotent or adult stem cells (precursor cells that
are naturally limited to becoming a specific tissue's cell types).
A next step with magnetic dendrimers,
Bulte says, is watching the cells' distribution when they are injected
into the circulatory system instead of the brain. Bulte also wants to study
white blood cells in diseases of the central nervous system, such as multiple
sclerosis, as well as the behavior of embryonic stem cells and stem cells
from bone marrow. (Stem cells from bone marrow and blood have been used
for decades in cancer treatments and more recently for some inherited metabolic
disorders.)
Other co-authors of the report are
Ian Duncan, Brian Witwer and Su-Chun Zhang of the University of Wisconsin
School of Veterinary Medicine; Erica Strable of Temple University; Joseph
Frank, Bobbi Lewis, Holly Zywicke, Brad Miller and Peter van Gelderen of
the NIH; and Bruce Moskowitz of the Institute for Rock Magnetism at the
University of Minnesota, Minneapolis. Bulte (NIH) and Douglas (Temple)
have applied for a patent on these magnetic dendrimers.
Related Web site:
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http://biotech.nature.com
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