By injecting a protein into mice with heart damage, researchers in Boston have shown that it’s possible to cause adult heart-muscle cells to proliferate and cardiac function to improve. The approach could eventually prove valuable for heart-attack patients who have lost cardiac-muscle cells and some cardiac function, especially since existing therapies are unable to regenerate or restore these lost cells.
Several large research groups are working on techniques to regenerate heart tissue or shore up heart function using stem cells, and some of these projects have reached clinical trials. The Boston team’s work, led by Bernhard Kühn at Children’s Hospital Boston, instead focuses on stimulating adult heart cells, an alternative approach that could, in theory, lead to less invasive and less expensive treatments.
Kühn’s work is “very exciting” in that it involves using “protein therapy to harness cardiac regeneration,” says Roger Hajjar, director of the cardiovascular research center at Mount Sinai Medical Center in New York, who was not involved in the research.
For years, the prevailing dogma was that adult cardiac cells do not regenerate. Some researchers have shown, however, that at least some cardiac cells are, in fact, capable of dividing. But following a heart attack, they do not proliferate sufficiently to repair the resulting damage. Kühn’s work suggests a novel way in which they could be stimulated to do so.
In a study published today in the journal Cell, Kühn and colleagues first showed that a protein called neuregulin1 can cause fully mature heart-muscle cells from mice to divide and proliferate in a petri dish. The researchers then injected this protein into mice with heart damage. After 12 weeks of daily injections, the animals’ hearts showed less hypertrophy, or enlargement, and improved function. For instance, the hearts had about a 10 percent increase in ejection fraction–the fraction of blood pumped out of the left ventricle with each beat. The treatment “didn’t make the damage go away completely,” says Kühn, “but it did make the heart work significantly better.”
Going forward, one potential worry is that Kühn’s team injected the protein systemically, meaning that it traveled throughout the animals’ bodies. In addition to the heart, cells in the breasts and nervous system also express receptors for the therapeutic protein, which raises the risk of unwanted cell division. “We were nervous about the treated mice developing breast tumors or producing milk,” Kühn acknowledges. “We did not see abnormalities when we looked at the breasts macroscopically. But we plan to study breast and nervous tissue,” more closely in future research, he says. A therapy that could be injected directly into the blood would be relatively easy and inexpensive to administer, he notes.