An unlikely brew of seaweed and glow-in-the-dark
biochemical agents may hold the key to the
safe use of transplanted stem cells to treat patients with
severe peripheral arterial disease,
according to a team of veterinarians, basic scientists and
interventional radiologists at Johns Hopkins.
In a preliminary "proof of concept" study in rabbits,
Johns Hopkins scientists safely and
successfully delivered therapeutic stem cells via
intramuscular injections and then monitored the stem
cells' viability once they reached their targets.
A report of the study by Johns Hopkins radiologists
was presented March 10 at the Society of
Interventional Radiology's 34th annual scientific
Stem cells hold promise in treating peripheral
arterial disease, or PAD, by reconstituting or
increasing the number of blood vessels to replace or
augment those choked off by plaque buildup. A
chronic condition that can lead to amputations and even
death, PAD is marked by vastly reduced
circulation of blood in vessels feeding the legs and other
"peripheral" body parts, and affects as many
as 10 million Americans. Many cases can be treated with
angioplasty or stents, similar to approaches
used in coronary artery disease, but for some patients with
extensive disease, conventional treatment
is not feasible, researchers say.
Among the technical hurdles to improving blood flow in
such patients, according to Dara L.
Kraitchman, associate professor of
radiology at Johns
Hopkins, is a means of telling doctors whether
injected stem cells are staying alive and reaching the
right targets to grow and develop into the
needed new tissue.
This is critical, Kraitchman said, because the body's
own immune defenses may recognize the
potentially helpful donor stem cells as foreign invaders
and try to destroy them, and also because
traditional radioactive labeling agents, or tracers, which
are normally used to track cells, can be toxic
to stem cells.
To overcome rejection of the stem cells by the body's
immune system — in this case, rabbit
immune systems — the researchers first created a
novel "capsule" derived from seaweed, which was
used to surround and protect the rabbit stem cells from
attack by the host's immune system. Within
the seaweed capsule, they added X-ray contrast agents to
allow the capsules to be seen on X-ray
angiography. Next, they engineered the stem cells within
the capsules to produce luciferase, the same
bioluminescent chemical produced by fireflies, which is
highly visible under bioluminescence imaging.
"Once we were able to trick the immune system into not
attacking the cells, we had to know
they arrived at their destination and were living,"
Kraitchman said. "We could use standard X-ray
angiography of blood vessels to see the transplanted cells.
When they lit up like fireflies at night, we
knew they were still alive."
Frank Wacker, director of Vascular Interventional
Radiology and visiting professor of radiology
at Johns Hopkins, said, "Hopefully, this new technology
will one day pave the way for treating humans.
We look to the day when we will be able to perform targeted
delivery of stem cells to treat PAD in
patients who may be facing amputation or death."
Collaborators on the project from Johns Hopkins are
Dorota Kedziorek, postdoctoral fellow in
Radiology; Piotr Walczak, assistant professor in Radiology,
Division of MR Research, Institute for
Cellular Engineering; Yingli Fu, postdoctoral fellow in
Radiology; Aravind Arepally, associate professor
of radiology; and Jeff Bulte, professor of radiology,
Division of MR Research, Institute for Cell
Engineering. The probe to enable the stem cells to produce
luciferase was provided by Stanford