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The newspaper of The Johns Hopkins University April 2, 2007 | Vol. 36 No. 28
Researchers Develop a Novel X-ray System to Track Stem Cells

By Gary Stephenson
Johns Hopkins Medicine

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 cellular therapeutics."

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.


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