However, others say that systemic injections would be too risky in people, especially since cancer cells might already be present in some patients. If this therapy were to move forward, it would be “extremely important to deliver the protein locally,” says Hajjar.
A few previous studies have also shown that proteins injected into animal models can cause division of adult heart cells and improvement in cardiac function. In 2007, Kühn found that a different molecule, a protein called periostin, also caused some cardiac-muscle cells to proliferate, improving heart function. In 2006, another group at Children’s Hospital Boston used a regimen with a protein called fibroblast growth factor and found that it too resulted in heart-cell proliferation, reduced scarring, and improved function.
Most animal and human studies have focused, however, on various kinds of stem cells. Many researchers believe that the adult heart contains a small number of tissue-specific stem cells, which could potentially play a role in regeneration and repair. Piero Anversa of Brigham and Women’s Hospital in Boston recently began phase-one trials for an approach in which cardiac stem cells are isolated from patients, expanded in the lab, and then reinjected. Anversa has shown that a cocktail of growth factors, injected into dogs, causes native cardiac stem cells to differentiate into mature cells and improve heart function. Meanwhile, Eduardo Marban, director of the Cedars-Sinai Heart Institute in California, has pioneered a related technique. His team removes small pieces of tissue from patients’ hearts, grows a collection of cells, including cardiac stem cells, and then injects the cells into patients’ coronary arteries.This work is also in phase-one trials.
Other researchers are focusing on stem cells derived from bone marrow. And in other research conducted in pigs and, preliminarily, in humans, the use of bone-marrow cell therapy has improved heart function.
One advantage of cell therapy is that the cells could be administered less often, in theory, than a drug or protein therapy, says Joshua Hare, director of the Interdisciplinary Stem Cell Institute at the University of Miami, although the administrations would also likely be more invasive. Several cell-therapy approaches are also further along in the research process and could potentially be available to patients sooner.
Still, there may be some overlap in how protein therapy and cell therapy could work in the heart. Some of the benefits of cell therapy may come from stimulating endogenous pathways similar to or the same as the one targeted by Kühn, says Hare. It’s possible that part of the underlying biology is similar, he adds, and “we just have to figure out the best way to manipulate it.”