Researchers at the Stanford University School of Medicine have developed a new visualization technique which they believe could eventually help make the repair of damaged hearts through regenerative medicine a reality.
In a study published in Wednesday’s edition of the journal Science Translational Medicine, senior author and Stanford radiology professor Sam Gambhir and colleagues describe how they plan to mark the stem cells which would be used in the repair process.
By marking the cells, doctors would be able to track them by using standard ultrasounds as they leave the needle and enter a patient’s body. The process would allow for the stem cells to be guided to their intended destination more precisely, and would also allow doctors to monitor them using magnetic-resonance imaging (MRI) technology for several weeks afterwards, the researchers explained.
To date, both human and animal trials in which stem cells were injected into cardiac tissue to treat severe heart attacks or heart failure have been largely unsuccessful, said Gambhir.
“We’re arguing that the failure is at least partly due to faulty initial placement,” he explained in a statement. “You can use ultrasound to visualize the needle through which you deliver stem cells to the heart. But once those cells leave the needle, you’ve lost track of them.”
For this reason, scientists have been unable to precisely determine whether or not the stem cells actually reached the heart wall, and whether they remained there or diffused away from the cardiac tissue. In addition, there has been no way to determine how long the cells managed to stay alive, or if they successfully replicate and eventually develop into heart cells.
Gambhir’s team method could help answer some of those questions.
“All stem cell researchers want to get the cells to the target site, but up until now they’ve had to shoot blindly,” he said. “With this new technology, they wouldn’t have to. For the first time, they would be able to observe in real time exactly where the stem cells they’ve injected are going and monitor them afterward.”
“If you inject stem cells into a person and don’t see improvement, this technique could help you figure out why and tweak your approach to make the therapy better,” Gambhir added.
In addition to the issues surrounding the initial position of the therapeutic stem cells, tracking them once they enter the body has proven troublesome since there is no way to distinguish them from any other cell in the patient’s body. Since they normally cannot be tracked upon entering the body, if the attempt to repair the heart fails, doctors often are unable to pinpoint exactly why the process proved unsuccessful.
The new technique, however, aims to solve those problems by using extremely small nanoparticles that act as imaging agents. The nanoparticles, which have a diameter slightly less than one-third of a micron (or less that one-thirtieth the diameter of a red blood cell), are made of silica so that they can be visualized by ultrasound. Furthermore, an MRI contrast agent known as gadolinium was also added to the imaging agents.
Gambhir and his colleagues were able to successfully demonstrate that mesenchymal stem cells – a class of cells frequently used in heart-regeneration research – could store the nanoparticles without sacrificing any of their ability to survive, replicate and differentiate into living heart cells.
Lead author Jesse Jokerst, a postdoctoral scholar in Gambhir’s lab, said there were concerns that the signal would be fairly weak. However, he and his colleagues found that once they were ingested, they clumped together within the cells, reflecting the ultrasound waves far more dramatically and providing a far stronger signal than anticipated.
Despite the optimism, it will probably be at least three years before the technique can be tested in humans.