Exosomes – A Potential Alternative to Stem Cells
for Treating Heart Attacks

By Adrienne Mueller, PhD
June 15, 2020

Heart attacks cause cardiomyocytes or heart cells to die. To help recover the lost heart tissue, recent research efforts have primarily focused on creating new cardiomyocytes from stem cells. Unfortunately, cardiomyocyte transplants have had limited success as a therapy. Yet in some cases even very small or poor transplants can improve heart function. Why that is the case is unclear, but in a study recently published in the Journal of the American Heart Association, a group of Stanford researchers sought to find out.

Led by first author Michelle Santoso and senior author Phil Yang, MD, Associate Professor of Medicine, the authors hypothesized that recovery might not be caused by the transplanted cells directly, but instead by something secreted by the normal or injured cardiomyocytes. Specifically, they investigated whether cardiomyocyte-secreted exosomes could be the actual source of improvements in cardiac function. Exosomes are vesicles containing numerous small molecules and are a means for cells to communicate with each other. If exosomes are sufficient to improve cardiac function this would explain why even small or poor transplants can sometimes cause cardiac improvement. They tested this hypothesis and found that – sure enough – exposure to exosomes was as effective as cardiomyocyte transplants in improving cardiac function in mice recovering from heart attacks.

The next question was, how are the exosomes improving cardiac function? One process that exosomes influence in neighboring cells is autophagy: a cell’s self-digestion. Although it seems counterintuitive, digesting their own material is part of a healthy cell’s life cycle, and previous work has shown that autophagy is dysregulated in unhealthy heart tissue. The authors demonstrated that cardiomyocyte exosomes increase autophagy and rectify the impaired autophagy exhibited by unhealthy heart tissue. Promoting autophagy is therefore an excellent candidate mechanism for how exosomes improve cardiac function.

The study by Santoso et al shows that it may not be necessary to subject patients with heart disease to the risks of stem cell transplants – and their uncertain outcomes. Instead, patients could potentially be treated with cardiomyocyte exosomes: an alternative cell-free, patient-specific therapy.

Several additional members of the Stanford Cardiovascular Institute contributed to this work including Gentaro Ikeda, Yuko Tada, Ji-Hye Jung, Evgeniya Vaskova, Praveen Shukla, Joseph C. Wu, Y. Joseph Woo. Other Stanford-affiliated contributing-authors include Raymond G. Sierra, Cornelius Gati, Andrew B. Goldstone, Daniel von Bornstaedt and Soichi Wakatsuki.

Michelle Santoso

Phil Yang, MD