The promise and challenges of cardiac regenerative medicine—facilitating the growth of new tissue to repair damage to the heart following a heart attack—received wide attention at CCC/Vascular 2013. The labs of University of Ottawa Heart Institute researchers Darryl Davis, MD and Erik Suuronen, PhD, were responsible for more than 20 presentations highlighting their continued progress in this area.
Early-phase clinical trials of cultured cardiac stem cells have shown a modest benefit in patients after an acute heart attack: at least as good as available drug therapies, according to Dr. Davis, an electrophysiologist and clinician-scientist who leads the Cardiac Translational Research Laboratory.
But even with the best available drug therapies, many patients develop heart failure after a heart attack because resulting scar tissue impedes heart function. Researchers are now trying to improve the healing capacity of our resident stem cells in the hope of preventing the formation of scar tissue. “We are looking at ways to enhance the healing hormones these stem cells produce,” said Dr. Davis. To do this, they need to understand how these proteins work by understanding which stimulate stem cell activity and which may actually interfere with healing.
Results presented at the conference by Dr. Davis’ lab highlighted several molecules that improved tissue repair in a mouse model of heart attack. When the researchers genetically engineered stem cells to produce these molecules in larger-than-normal quantities, some increased the production of new blood vessels at the site of cardiac injury while others promoted the development of new heart muscle cells.
Eventually, these promising molecules may be genetically engineered into a patient’s own stem cells to help to reverse major cardiac damage and heart failure. The Heart Institute recently treated the first patient in the first ever clinical trial to use this approach. In this case, researchers genetically reprogrammed stem cells, derived from the patients’ own blood, to produce more of a key healing molecule.
Another aspect of tissue regeneration involves protecting the fragile stem cells so that they can attach to and survive at the site of injury. Only 10 to 15 per cent of stem cells injected into damaged hearts are retained at the site after one hour, explained Dr. Davis. One study from his team showed, in a mouse model of heart attack, that encapsulating stem cells within a supportive “cocoon” produced a three-fold increase in cells retained up to three weeks after injection. Transplanted stem cells were better able to graft to the damaged site and develop into working heart tissue, further boosting cell-mediated cardiac repair.
Protective biomaterials are the main focus of Suuronen’s Cardiovascular Tissue Engineering Laboratory. The supportive injectable gels his team uses are made of collagen and have shown promise in encouraging the stem cells that make new blood vessels—called circulating angiogenic cells, or CACs—to migrate and go to work at the site of cardiac injury.
In research presented at the conference, his team focused on how, at a molecular level, their biomaterials encourage CAC activity. A broad understanding of which beneficial cellular signalling pathways are turned on by the biomaterials could help the researchers add components that further encourage regenerative activity. Work presented by Dr. Ali Ahmadi, a doctoral student in the Suuronen lab, examined a protein in one such signalling pathway and placed as first runner up for the CCC Trainee Research Award in Basic Science.
“These materials are very easy to manipulate—you could add proteins, sugar groups, growth factors. There are lots of modifications that can be made as we find out what it is we need to add to them to make them work better,” said Suuronen.
Biomaterials are being developed for many cardiac applications, but they may first see use in the clinical setting to target patients with established scar tissue: “They’re at higher risk for heart failure,” explained Suuronen, “and the treatments available for them are fewer and less effective.” One study they presented at the conference showed that a biomaterial consisting of chitosan—a carbohydrate derived from shellfish—added to collagen improved heart function in a mouse model of scar tissue caused by a heart attack.
Both labs also presented findings on factors that appear to decrease the healing capabilities of stem cells, including diabetes, aging, risk factors for coronary artery disease, and heart attack itself. This information offers new ways to augment both the stem cells and the biomaterials that could protect them.
The Suuronen and Davis labs each will have multiple presentations at the upcoming American Heart Association Scientific Sessions to be held in Dallas.