Multimodality imaging tracks cardiac stem cell therapies

PET, SPECT, MRI, and even x-ray-based modalities are helping researchers learn how to use stem cells to restore the pumping power of injured hearts. The modalities factor into plans to track stem cell delivery, survival, and replication during clinical use, making them essential for research.

That was the take-home message delivered by Dr. Joseph Wu, an assistant professor of medicine and radiology at the Stanford University School of Medicine, at the 2009 SNM Symposium on Multimodality Cardiovascular Molecular Imaging in Bethesda, MD.

Evidence keeps accumulating on the potential benefits of stem cell therapy to restore myocardial function after a heart attack, though most of it comes from small-animal studies. Multiple studies involving humans have recently started, but basic questions related to cell survival, function, and mechanisms of improvement in human patients are still not well appreciated, Wu said.

"The rapid translation into clinical medicine has left many questions unresolved, which underscores the importance and utility of using molecular-based imaging modalities to monitor stem cell survival and behavior in vivo," Wu said.

Cardiac stem cell therapy poses three major challenges for researchers:
• Improve immunosuppression and cell transplantation tolerance
• Understand the tissue-reproducing ability of specific cell types
• Evaluate new approaches to improve stem cell therapy's efficacy, particularly in terms of long-term cell survival

Imaging could be a valuable tool to researchers in all three areas, Wu said.

He cited studies conducted at Stanford and other institutions that have used PET, SPECT, or MRI to reveal, for instance, survival or immunosuppression patterns. He also mentioned studies that have used imaging to determine what human cell types -- ranging from bone marrow to mesenchymal to embryonic and including induced pluripotent stem cells -- could be better suited for cardiovascular repair. New studies relying on imaging as an end-point will focus particularly on embryonic and induced pluripotent stem cells, he said.

A large number of stem cell therapy trials on cardiac repair have used more conventional imaging modalities, such as ultrasound and MRI, to monitor the procedure, said Dara L. Kraitchman, Ph.D., an associate professor of radiology at Johns Hopkins University, who presented another lecture.

Two common issues persist, according to Kraitchman. Researchers still have trouble "seeing" the exact location of cells after injection, and a large number of cells die after transplantation. Recent studies performed at Hopkins have proposed a solution: labeling stem cells with radiopaque agents within microcapsules to allow visualization and tracking with conventional x-ray fluoroscopy or CT.

The technique has shown promise, and researchers are taking it to the next level by fusing the x-ray-based angiography procedure with MRI. The hybridized "XFM" tracking technique brings together the best of both worlds and is being used at Hopkins in collaboration with interventional cardiology partners, Kraitchman said.

"Stem cell therapy is promising," Wu said. "But a lot of work needs to be done."