Iron Particles, MRI Could Replace Biopsies to Track Stem Cell Therapy and Deploy Stents, Animal Studies Show
Related News: Stem Cell ResearchIn a series of experiments in animals, researchers at Johns Hopkins have successfully used a technique that tracks mesenchymal stem cells via magnetic resonance imaging (MRI) to monitor the progress of the cells in repairing tissue scarred by heart attack.
The Hopkins findings, presented in November at the American Heart Association’s Scientific Sessions and published in a supplement to the journal Circulation, are believed to be the first demonstration of how the technique, which labels the cells with minuscule iron oxide particles, can be used to assess the clinical benefit - if any - of cell-based therapies.
According to senior investigator and veterinary radiologist Dara Kraitchman, V.M.D., Ph.D., "The technique has potentially broader applications and benefits for patient care because MRI technology is widely available and avoids the discomfort and risk of infection from biopsies, the standard method used in therapy checkups."
In a related study, also presented at the meeting, the Hopkins team showed that a more advanced technique used with MRI, called inversion recovery with on-resonant water suppression, or IRON for short, could be used to monitor iron-labeled stem cells and to guide deployment of a stent, a device that widens arteries at risk of clogging and prompting a heart attack.
Previous Hopkins research on animals whose hearts had been injected with adult stem cells showed that heart function was restored to its original condition within two months, and more than 75 percent of dead scar tissue disappeared, having been replaced with healthy-looking heart tissue. Clinical studies are now under way at Hopkins and elsewhere to find out if similar benefits result in humans.
The researchers made stem cells visibly distinct from all others by labeling them with a metallic compound made up of iron oxide nanoparticles, one thousandth of a millimeter in diameter, which can be permanently taken up within cells and, unlike most other metals, seen by MRI.
In the latest study, 13 dogs underwent surgery to create heart muscle damage similar to what happens in a naturally occurring heart attack. Six were treated with iron-oxide-labeled stem cells and seven served as study controls, receiving no stem-cell injections.
Mesenchymal bone marrrow stem cells, known to give rise to a variety of cell types, were injected across three regions of the hearts to find out if injecting one region or another made a difference in how well the heart recovered. The sites included heart-attack-damaged muscle consisting of mostly dead scar tissue, and normal, undamaged heart tissue, as well as tissue at the border area between the scar and normal tissue, called the peri-infarction zone.
Kraitchman, an associate professor at The Johns Hopkins University School of Medicine, says that in the peri-infarction zone, some life remains in the tissue, including a working vascular supply with some capillaries.
For two months after injection, the animals were monitored by cardiac MRI at weekly intervals.
The damaged area decreased significantly, by 20 percent in both groups, showing that healing had occurred. However, the size, or mass, of left ventricular tissue decreased by 2.5 percent in the stem-cell group, while the control group lost more than 20 percent of its mass, indicating that the stem-cell-treated hearts were maintaining their muscle strength during the healing process while control hearts were showing steady signs of failure and reduced function.
MRI also showed that stem cells were incorporated into the heart tissue itself, mostly in the peri-infarction zone. Measurements of the heart’s pumping function also improved in the same region.
Posted on December 12, 2005 03:59 PM