Diagnostics & Imaging Week National Editor
How do you make sure injected stem cells are "happy"?
Put 'em in a bubble . . . made of seaweed, says Dara Kraitchman, MD, VMD.
After making sure they're happy, how do you keep track of them, watch how they're doing and doing what they're supposed to do when they arrive at their destination?
Give 'em a glow, she says.
Those are peculiar-sounding strategies employed by Kraitchman and her partner researchers at Johns Hopkins University (Baltimore), in a proof-of-concept study of a potential stem cell delivery method for treating peripheral artery disease (PAD).
"We have been very keen on being able to protect and track" the materials used in this type of therapy, she said.
The initial work was done with rabbits, which were given intramuscular injections of stem cells, the stem cells then monitored, as they remained viable and reached their target sites.
The study suggests some of the very diverse, often novel approaches being used these days in interventional radiology, a sector marked by an increasing number of applications – though generally invisible to the public and patients.
Kraitchman, associate professor of radiology at Hopkins, presented the study at last week's annual scientific meeting of the Society of Interventional Radiology (SIR; Fairfax, Virginia) in San Diego, and then further discussed some of its key strategies with Diagnostics & Imaging Week.
The researchers began with the understanding that some peripheral artery disease conditions have moved far beyond the ability of standard strategies to treat them: first drugs, then angioplasty and stenting, to push open the plaque in the blocked arteries of the legs.
But when the vasculature has deteriorated beyond help from these treatments, stem cells may have the ability to "retrofit" this system, by rebuilding the damaged vessels or by building alternative vessel systems to augment the circulation that still remains.
Easily said, not so easily done with real success, Kraitchman told D&IW.
The primary problems, she said, are in keeping a body's immune system from identifying stem cells as enemies and rejecting them, and then being able to know if the stem cells have indeed remained viable and, most important of all, have reached their target destination.
The first of these problems was solved by the researchers creating small seaweed capsules to hold and protect the stem cells so they are not seen as harmful invaders.
She said that, while odd-sounding, this approach wasn't any sort of "wow factor," but simply the extension of a previous method that has been explored in transplantation work.
The seaweed used is a form of alginate, already often used in medicine, such as in the delivery of islet cells for the treatment of kidneys, as a treatment for diabetes, itself often marked by extensive damage to lower leg vasculature and amputation.
"We've created this bubble" for the cells, Kraitchman said, her straight-forward explanation of the strategy for maintaining their viability. "They're happier inside the bubble."
Addressing the issue of tracking and monitoring these cells as they head to and find their destination, the researchers did not want to use the usual labeling agents. Such agents, such as traditional radioactive labeling solutions, or tracers, she said, are toxic to stem cells.
To change up the tracing strategy, the seaweed/alginate capsules served a second purpose.
Within the seaweed capsule, the researchers 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.
Kraitchman said the research team then used 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."
She indicated that the research is actually now somewhat beyond the very basic stage.
It is being supported by a five-year grant from the National Heart, Lung & Blood Institute of the National Institutes of Health, and she said that the work has progressed well into the second year. She hopes that the method will advance to human trials by year five, with "talking to the FDA" already in progress.
Overall, Kraitchman said, the goal is to create an "off-the-shelf" method of delivering stem cell products because of the fairly short time-line for creating, storing and using stem cells.
She said that the initial work focused on PAD, since the delivering could be made via injection, thus working systemically, but she hopes that the strategy could be used in more pinpoint therapy, such as for the liver and pancreas, using some sort of device to make a direct injection.
Underlining the diverse expertise behind the work, collaborating researchers came from the radiology, MR imaging, and cellular engineering units at Johns Hopkins, and the probe to enable the stem cells to produce the luciferase was provided by Stanford University (Stanford, California).
Images of the X-ray-visible stem cells are available at: www.hopkinsmedicine.org/Press_releases/2009/03_10_09.html.