The Secret to Mending a Broken Heart

When someone suffers a heart attack, part of the heart’s muscle cells are deprived of oxygen and die. They become encased in scar tissue. And they don’t come back. A top priority among researchers, therefore, has been finding a way to grow new heart muscle.

But the heart is a complex organ, and even as research moves forward questions remain how best to regenerate heart muscle cells. One such method has focused on injecting cells called cardiosphere-derived cells, or CDCs, directly into the damage site. And yesterday, a new study out of the Cedars-Sinai Heart Institute offered strong evidence as to how this method might actually work.

In the latest issue of Stem Cell Reports, a team led by Institute Director Dr. Eduardo Marban discovered that it’s not the CDCs themselves that are able to regenerate the cells—but rather molecules hidden inside, called exosomes.

Made up of many proteins stitched together, exosomes are involved in critical cellular processes, such as cell-to-cell communication. And though they were first discovered more than 30 years ago, scientists are just beginning to understand how they could be used to develop therapies. As Marban explained in a recent news release:

“[In this study] we have found that exosomes and the cargo they contain are crucial mediators of stem cell-based heart regeneration, and we believe this might lead to an even more refined therapy using the ‘active ingredient’ instead of the entire stem cell.”

In laboratory experiments, the team mimicked the effects of a heart attack on mice under anesthesia and then injected the mice not with the CDCs—as has previously been done—but with exosomes extracted from the CDCs. To their surprise, they found that the injecting exosomes—and exosomes alone—spurred muscle cell regeneration. And upon further examination, the team identified the elusive ‘crucial cargo:’ a tiny molecule called miRNA-146a that seemed to be calling at least some of the shots.

Marban and his team have reasoned that this molecule, and likely several others like it within the exosomes, are the driving force behind muscle cell regeneration. And in the future as they peel away more layers they could identify the exact molecular cocktail that spurs regeneration—which can then serve the basis for much-needed therapies.

Dr. Deepak Srivastava, an expert in cardiology and regenerative medicine at the Gladstone Institutes who was not involved in the study, was also encouraged by these results. As he recently told CIRM:

“This work raises the interesting possibility that cells could be used as a vehicle for delivery of therapeutic exosomes, and could even be manipulated to enhance delivery of desired therapies to damaged tissue. It will be important for this work to be reproduced and to determine the precise factors within the exosomes that account for the positive effects observed in mice.”

These findings come on the heels of the announcement that Capricor Therapeutics, a biotechnology company focused on developing therapies to treat heart disease, has entered into an exclusive agreement with Cedars-Sinai Medical Center to license exosomes originating from CDCs. CIRM has also seen the potential for CDCs, last year announcing the funding of a phase 2 trial for a treatment developed by Capricor.

Marban and his team are optimistic about these initial results, and how they could be used to develop therapies that don’t involve the injection of cells into the heart. As he told CIRM:

“We are very keen on the concept that exosomes may be useful as cell-free therapeutic agents. Although human studies using CDCs are ongoing, I want to develop exosomes as next-generation therapeutic agents.”

Anne Holden