Repairing the Heart with Stem Cell-Derived Exosomes

Myocardial infarction, also known as heart attack, can be a devastating or even deadly event. It occurs when blood flow in one or more coronary arteries is blocked. Since coronary arteries supply blood to the heart muscle, a blockage in a coronary artery prevents oxygen and nutrients from reaching heart tissue.

While the heart can sustain short periods of time without oxygen or nutrients, heart cells become dysfunctional and die if blood flow is not restored within several hours. While clot-busting drugs, percutaneous intervention (PCI), and balloon angioplasty have provided a way to restore blood flow to the heart during a heart attack, once heart cells die there is no way to bring them back. Since most heart tissue is cardiac muscle, dead heart tissue cannot participate in the contraction or squeezing of the heart during a heartbeat. Thus, people who have survived a heart attack are often left with poor heart function (e.g. congestive heart failure).

Stem cell researchers have begun to question whether heart tissue destroyed during a heart attack is necessarily gone forever. Research is beginning to show that stem cells given after myocardial infarction are able to improve the squeezing power of the heart. By extension, stem cell treatment is able to improve the abilities heart to pump blood throughout the body.

Researchers initially assumed that it was the stem cells themselves that became new heart cells, replacing dead and dysfunctional heart tissue. While there is evidence that this occurs, it seems that stem cells play an even bigger role in heart tissue repair than simply becoming new heart cells. Stem cells release small packets of a material called exosomes and microvesicles. Exosomes and microvesicles hold proteins, cytokines, chemokines, growth factors, DNA, messenger RNA, and micro RNA. Researchers now believe that these materials hold the true power of stem cells in cardiac repair and regeneration.

Various types of stem cells produce exosomes that could potentially help repair a damaged heart. While cardiac stem cells may seem like an obvious source for these exosomes, induced pluripotent stem cells and mesenchymal stem cells are also capable of releasing exosomes that are potentially beneficial in cardiac repair.

Stem cells—or more accurately the exosomes contained within the stem cells—help repair damaged heart tissue in several ways. Stem cell-derived exosomes contain factors that promote the survival of vulnerable heart cells and cells that are dysfunctional after a heart attack (but not dead). Exosomes also help new blood vessels to form in and around the damaged heart muscle in a process called angiogenesis. These new blood vessels deliver oxygen, nutrients, and molecules that help support the growth and function of heart tissue. Exosomes also appear to promote a healthy immune system response after a heart attack, rather than a destructive inflammatory reaction. In other words, the materials found in exosomes guide the immune system to clear away damaged tissue without creating extensive fibrotic (i.e., tough, nonfunctional) tissue.

While most clinical trials thus far have studied the effects of stem cells directly infused into humans after myocardial infarction, exosomes are rapidly becoming the focus of future clinical trials in this area.