SIR 2009: Bioluminescence Imaging Agent Allows View of Stem Cell Efficacy in PAD

Kristina Rebelo

March 12, 2009

March 12, 2009 (San Diego, California) — A novel X-ray-visible stem-cell therapy for the treatment of peripheral arterial disease (PAD) enables targeted delivery of cellular therapeutics, thereby eliminating the need for systemic injection of large amounts of the reporter probe, according to a study presented here at the Society of Interventional Radiology 34th Annual Scientific Meeting.

The new technique assists in creating new or additional blood vessels for individuals with extensively narrowed or clogged arteries by allowing simple imaging to view and locate transplanted stem cells in the PAD patient.

Johns Hopkins interventional radiologists are using C-arm computed tomography (CT) for image-guided delivery in the angiography lab to precisely target stem-cell delivery in relation to blood vessels, without transferring to a separate CT scanner, where X-ray agents are toxic to stem cells.

Stem-cell therapy may provide a new weapon to fight PAD, according to researchers, a disease that affects 12% to 20% of Americans aged 65 years and older; 20% of these patients have a narrowing of the vessels, some quite severe, according to researchers.

Borrowing a Trick From the Firefly

Dr. Dara Kraitchman

"We are creating new vessels with cellular products by borrowing a trick from the firefly — a suitable noninvasive method to track the fate of stem cells in the body," study coauthor Dara L. Kraitchman, VMD, PhD, FACC, associate professor, Department of Radiology, Johns Hopkins University School of Medicine, in Baltimore, Maryland, said during a news conference. "We inject the cells to where the blood supply is lost and recruit new cells, but the problem with current therapy is you cannot see where the cells are injected, and a large number of cells die after administering the injection, leaving only about 5% live cells after 24 hours. That's a tremendous waste of resources."

Dr. Kraitchman said her collaborators tested the method in a rabbit model the first time. They used bone-marrow stem cells from New Zealand white rabbits that were transfected with tri-fusion multimodality reporter genes containing red fluorescence protein, truncated thymidine kinase (SPECT/PET reporter), and firefly luciferase (bioluminescence imaging [BLI] reporter).

Luciferin is the chemical substance present in the cells of bioluminescent organisms, such as fireflies. Microencapsulation of the chemicals allowed the creation of X-ray-visible capsules. Rabbits received intramuscular injections; injection sites were documented using standard fluoroscopy postinjection and again within the first 3 days after injection. BLI technology was used to evaluate cell survival.

Study authors report no major adverse events in their BLI protocol, which demonstrated a 35% to 45% reduction in signal intensity, compared with the unlabeled capsules.

"The application for these smarter therapies will be in elderly populations where this protective capsule will tell us that cells are within the alginate [seaweed] capsule or 'bubble'; fewer cells will have to be injected," said Dr. Kraitchman. "These bubbles can be transplanted into a leg, for instance, and can then be placed accurately at blocked blood vessels that need intervention."

Stem Cells Visible Like a Firefly at Night

Even with X-ray imaging, researchers previously could not determine if the stem cells had remained alive and functioning, she said. With the BLI imaging agent produced by fireflies, they could see the stem cells that remained alive, "much like a firefly at night."

Michael S. Stecker, MD, from the Department of Vascular and Interventional Radiology at Brigham and Women's Hospital, in Boston, Massachusetts, said he was impressed with the technique presented by Dr. Kraitchman.

"A lot of people are doing this gene-cell work and injecting the cells, but they don't know where they're going," said Dr. Stecker, "but what I got from this encapsulated stem-cell technique is that now you can see where you put the cells with almost any imaging modality."

Dr. Kraitchman reports a financial relationship with Boston Scientific Corporation and Bayer Schering Pharma AG. Dr. Stecker has disclosed no relevant financial relationships.

Society of Interventional Radiology (SIR) 34th Annual Scientific Meeting: Abstract 133. Presented March 10, 2009.

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