Most classes of therapy benefit from some form of targeting or selectivity, helping to direct them to the tissue of interest, and away from other places where they might cause side-effects. Cells are difficult to work with, but they are also much more capable of selective targeting, since they can migrate. Many types of cell reliably find their way from one part of the body to another in the course of their functions, but where no suitable mechanism exists in human biochemistry, it is sometimes possible to look elsewhere. Here, researchers adapt a bacterial targeting system and apply it to the stem cells that might be used in regenerative therapies for damaged heart tissue.
To date, trials using stem cells, which are taken and grown from the patient or donor and injected into the patient's heart to regenerate damaged tissue, have produced promising results. However, while these next generation cell therapies are on the horizon, significant challenges associated with the distribution of the stem cells have remained. High blood flow in the heart combined with various 'tissue sinks', that circulating cells come into contact with, means the majority of the stem cells end up in the lungs and spleen.
"We know that some bacterial cells contain properties that enable them to detect and 'home' to diseased tissue. 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 team developed the technology by looking at how bacterial cells use a protein called an adhesin to 'home' to heart tissue. Using this theory, the researchers were able to produce an artificial cell membrane binding version of the adhesin that could be 'painted' on the outside of the stem cells. In an animal model, the team were able to demonstrate that this new cell modification technique worked by directing stem cells to the heart in a mouse.
"Our findings demonstrate that the cardiac homing properties of infectious bacteria can be transferred to human stem cells. Significantly, we show in a mouse model that the designer adhesin protein spontaneously inserts into the plasma membrane of the stem cells with no cytotoxity, 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."