In a first of its kind study, researchers at Johns
Hopkins Medicine have developed a new technique that
transports therapeutic stem cells in a multilayer
microcapsule that not only protects the cells from being
attacked by the body's immune system but also enables them
to be seen on X-ray.
Results of the study were presented at a Late-Breaking
Emerging Technologies and Innovations session on Sunday,
March 25, at the American College of Cardiology annual
meeting in New Orleans.
Using microcapsules, dubbed XCaps, that are visible
using X-ray imaging techniques, the researchers were able
to track the delivery, survival and function of donor stem
cells used to treat cardiovascular disease in rabbits.
"In acute ischemia, you don't have the luxury of
taking stem cells from the body and waiting two to three
weeks to culture and expand them in the laboratory," said
Dara L. Kraitchman, an associate professor of radiology at the School
of Medicine. "Ideally, we'd like to be able to take donor
cells off the shelf, make them X-ray visible, protect them
from the immune system and deliver them precisely where we
want them to be."
The researchers created the XCaps by coating donor
stem cells with layers of alginate, a compound that
provokes little immune response; barium, a contrast agent
that makes the microcapsule X-ray visible; and
poly-L-lysine, which holds the microcapsule together. The
outer coating is made up of another layer of alginate.
The researchers replicated the effects of severe
peripheral arterial disease in 13 female rabbits by
inserting a platinum coil in the artery supplying blood to
the hind limbs of the animals. One day later, the female
rabbits were randomly assigned to receive an injection of
XCaps created from the stem cells of male rabbits, XCaps
without stem cells, stem cells alone or a sham injection.
XCaps were visible on X-ray both immediately after
injection and at two weeks, allowing the researchers to
monitor the delivery and disposition of the XCaps.
Kenyatta Cosby, a postdoctoral fellow at Johns
Hopkins, said, "The nice thing about XCaps is that you can
see each individual capsule very clearly on X-ray. We also
observed no accumulation of fibrous material around the
capsules, which suggests a minimal immune response."
Added Kraitchman, "Since XCaps can be made using
FDA-approved clinical-grade compounds, they represent the
first potentially biocompatible therapy that will enable
X-ray visualization of stem cells to assist in targeting
Other members of the research team are Aravind
Arepally, Brad Barnett, J.W.M. Bulte, Wesley Gilson, Gary
Huang and Grigorios Korosoglou, all of Johns Hopkins; and
Lawrence Hofmann, of Stanford University.