Researchers at the Institute of Biomedical Engineering at the University of Toronto have demonstrated a new way to monitor transplanted stem-cell-derived heart cells using magnetic resonance imaging (MRI). The method allows researchers to visualize where transplanted cells survive over time, which could help scientists evaluate and improve emerging stem cell therapies for heart damage such as those caused by heart attacks.
Professor Hai-Ling Margaret Cheng and her team have shown that an imaging platform known as “bright ferritin MRI” can be used to track transplanted human pluripotent stem cell-derived cardiomyocytes in the hearts of rats for up to eight weeks. The findings were published in a recent issue of Magnetic Resonance in Medicine .
Human pluripotent stem cell-derived cardiomyocytes can form new heart muscle and integrate with existing tissue. However, many transplanted cells do not survive in clinical trials, and researchers currently lack reliable tools to monitor transplanted cells over long periods inside the body. Existing imaging methods either work only in small animals, or rely on labels that fade or produce misleading signals as cells divide or interact with the immune system.
“Tracking therapeutic cells inside the living body has been a scientific endeavour for decades,” says Cheng.
“The gap in the field, however, has been a failure to visualize surviving cells without losing signal beyond a few days or weeks, and with sufficient signal. Our goal is to address these critical gaps. We want to visualize and spatially map therapeutic cells as long as they are alive, wherever they are in the body.”
To test the approach, lead author Keyu Zhuang and colleagues engineered stem cells to overexpress ferritin, a protein that stores iron in cells. These modified stem cells were then differentiated into cardiomyocytes and assessed in laboratory experiments to confirm that they maintained normal cell structure, contractile proteins and electrical properties.
The researchers then transplanted the engineered cardiomyocytes into the left ventricular heart muscle of immunodeficient rats, including animals with heart injury. Using MRI scanners, the team tracked the cells over eight weeks.
By administering manganese chloride, the researchers could trigger a bright MRI signal from the ferritin-expressing cells, allowing them to map the location of surviving transplanted cells in three dimensions. The MRI findings were confirmed using tissue analysis after the experiments. Additional echocardiography tests showed that the manganese treatment did not impair overall heart function.
“The next step is to use the information garnered from the bright-ferritin cell tracking technology to optimize stem cell research directly,” says Cheng.
“Now that we can reliably pinpoint when and where stem cells are surviving, stem cell scientists are better equipped to develop strategies for increasing cell survival.”
Magnetic Resonance in Medicine