Published online Sep 26, 2016. doi: 10.4252/wjsc.v8.i9.297
Peer-review started: May 27, 2016
First decision: July 6, 2016
Revised: July 12, 2016
Accepted: July 20, 2016
Article in press: July 22, 2016
Published online: September 26, 2016
Processing time: 116 Days and 4.2 Hours
Mesenchymal stem cells (MSCs) have been used to treat patients suffering from acute myocardial infarction (AMI) and subsequent heart failure. Although it was originally assumed that MSCs differentiated into heart cells such as cardiomyocytes, recent evidence suggests that the differentiation capacity of MSCs is minimal and that injected MSCs restore cardiac function via the secretion of paracrine factors. MSCs secrete paracrine factors in not only naked forms but also membrane vesicles including exosomes containing bioactive substances such as proteins, messenger RNAs, and microRNAs. Although the details remain unclear, these bioactive molecules are selectively sorted in exosomes that are then released from donor cells in a regulated manner. Furthermore, exosomes are specifically internalized by recipient cells via ligand-receptor interactions. Thus, exosomes are promising natural vehicles that stably and specifically transport bioactive molecules to recipient cells. Indeed, stem cell-derived exosomes have been successfully used to treat cardiovascular disease (CVD), such as AMI, stroke, and pulmonary hypertension, in animal models, and their efficacy has been demonstrated. Therefore, exosome administration may be a promising strategy for the treatment of CVD. Furthermore, modifications of exosomal contents may enhance their therapeutic effects. Future clinical studies are required to confirm the efficacy of exosome treatment for CVD.
Core tip: Exosomes are membrane vesicles that contain and transport specific bioactive molecules, such as proteins, messenger RNAs, and microRNAs, to recipient cells. In this review, we describe the mechanisms of exosome biogenesis, selective sorting of bioactive molecules into exosomes, and exosome secretion. We also discuss preclinical studies in which stem cell-derived exosomes were successfully used to treat cardiovascular disease (CVD). Finally, we discuss the future possibility of exosome-based clinical treatment of CVD.