An advance that could significantly reduce the burden of chronic illness and death from cardiovascular disease would be to eliminate the scars that damage the heart muscle, impairing the heroic work of this organ.
Dr. Reza Ardehali, a UCLA associate professor of medicine (cardiology), heads a group of researchers exploring novel therapies to deliver stem cell-derived heart cells to replace scars formed after a heart attack.
Scar tissue is a leading cause of arrhythmia, heart failure and sudden cardiac death.
In a major heart attack, a person loses an estimated 1 billion heart cells, which results in permanent scarring of the heart tissue. Loss of cell elasticity happens as part of aging as well, similar to how skin changes and sags over time.
Scarring causes several functional problems for the heart:
“A scar in the heart takes the place of cardiomyocytes – heart cells that beat,” says Dr. Jake Lusis, professor of medicine, human genetics, microbiology, immunology and molecular genetics at UCLA. “At a minimum, this makes the heart less efficient. In the worst-case scenario, it can short-circuit the heart’s electrical system.”
Reversing scarring, or preventing it in the first place, has been one of the major challenges of cardiovascular research, says Dr. Arjun Deb, an associate professor of medicine (cardiology) and senior author of a UCLA study published in 2014 in Nature.
The study found that the fibroblasts that form a scar also have the ability to regenerate healthy blood vessel cells in the heart. An overview of the study includes the following:
Dr. Deb is currently looking for such an agent. “Critical time windows are important for other cardiac lifesaving drugs such as tPA (tissue plasminogen activator). We are working on identifying critical time windows for modulating scar tissue,” he says.
In the process of seeking ways to regenerate, or “turn back the clock,” from heart damage, Dr. Deb and his group have studied the life cycle of scars. They have learned that the older scars get, the more they harden, or calcify.
The biology of scars and how they behave with time may be important for determining long-term heart function. Investigators have observed:
Dr. Deb says that there are remarkable similarities in the process of scarring in different organs after injury. His hope is that our findings and the therapeutic approaches we are developing can be used to treat scar tissue in other organs as well.
Other UCLA researchers are working on ways to mend hearts through regeneration and cell therapy.
Dr. Ardehali treats patients with advanced heart disease, while also studying ways to cure or reverse heart disease. Currently, mechanical circulatory support devices and heart transplants are the last options for patients with end-stage heart disease. The limited therapies available to such patients motivated Dr. Ardehali to investigate a regenerative approach to restore heart function.
Dr. Ardehali believes it will one day be possible to offer alternative therapies by delivering stem cells to regenerate the damaged heart.
The process might work this way:
This technique could benefit patients with the following conditions:
Dr. Ardehali and his team are actively working to make his vision a reality. His collaborators include UCLA stem cell biologists, cardiologists, bioengineers, developmental biologists and cardiac surgeons, among others.
Dr. Ardehali has identified a unique type of stem cells that can create heart cells and has successfully used new techniques to track transplanted cells via imaging. Recent discoveries include:
UCLA researchers have shown that although the rate of retention is very low – less than 10% of the cells engraft and integrate – some cells survive. Investigators have documented the cells’ differentiation into cardiac muscle and into vascular cells in the heart.
These therapies are still at an experimental level in the laboratory. Many hurdles still need to be overcome prior to clinical application. Still, Dr. Ardehali regards the progress to date as a “very promising first step to repopulate the heart in the hope of restoring its normal function.”