Researchers at the University of Bristol have developed a way to make stem cells move toward heart tissue when they are injected intravenously. The treatment could improve the efficacy of stem cell therapies for heart disease, which are currently hampered when most injected cells are filtered out of circulation by organs such as the lungs and spleen.
Stem cell therapies have enormous promise for regenerative medicine, including treatments to heal damaged cardiac tissue. However, so far, simply injecting cells intravenously or even into the heart tissue itself hasn’t worked all that well. Stem cells tend to be removed out of circulation by the body, and even cells directly injected into the heart don’t seem to want to stick around for long.
These Bristol researchers wanted to develop a way to make stem cells be attracted to cardiac tissue, in the hope that this will improve their therapeutic effects. “With regenerative cell therapies, where you are trying to treat someone after a heart attack, the cells rarely go to where you want them to go,” said Dr. Adam Perriman, a researcher involved in the study. “Our aim is to use this technology to re-engineer the membrane of cells, so that when they’re injected, they’ll home to specific tissues of our choice.”
To achieve this, the researchers turned to an unlikely source – bacteria. “We know that some bacterial cells contain properties that enable them to detect and ‘home’ to diseased tissue,” explained Perriman. “For example, the oral bacterial found in our mouths can occasionally cause strep throat. If it enters the blood stream it can ‘home’ to damaged tissue in the heart causing infective endocarditis. Our aim was to replicate the homing ability of bacteria cells and apply it to stem cells.”
The researchers created an artificial version of adhesin, a protein that bacteria use to home to heart tissue. They covered stem cells in the artificial protein and then tested them in mice, demonstrating that the modified stem cells naturally gravitated toward cardiac tissue.
“Our findings demonstrate that the cardiac homing properties of infectious bacteria can be transferred to human stem cells,” said Perriman. “Significantly, we show in a mouse model that the designer adhesin protein spontaneously inserts into the plasma membrane of the stem cells with no cytotoxicity, and then directs the modified cells to the heart after transplant. To our knowledge, this is the first time that the targeting properties of infectious bacteria have been transferred to mammalian cells.”
Study in Chemical Science: Designer artificial membrane binding proteins to direct stem cells to the myocardium