Therapeutic properties of stem cell-derived exosomes in ischemic heart disease

Ischemic heart disease is the most prominent cause of death worldwide. Current treatment options have shown limited success in preventing morbidity and mortality and the need for alternative therapeutic options is evident. Accumulating evidence points to the rising role of stem cell-derived exosomes as potential sources for treatment of ischemic heart disease. Exosomes are nano-scale (50-150 nm), membrane-bound extracellular vesicles that contain a variety of proteins, nucleic acids, lipids, and metabolites and can be released from almost every cell type in the body, including but not restricted to cardiac cells, immune cells, and stem cells. In this review exosomes derived from stem cells which may have potential application in ischemic heart disease are classified based on their source: mesenchymal, adipose, cardiac, and circulating endothelial progenitor stem cells. Alterations in exosome cargo, for instance through regulation of certain miRNAs, may regulate the cross-talk among cardiac cells and usually result in enhanced cardioprotective properties through various signaling mechanisms, leading to enhancement of angiogenesis, prevention of apoptosis and reducing fibrosis. However, many critical challenges remain in translation of exosomes-assisted therapies such as lack of a unified method for exosome isolation and characterization, finding the optimal cell culture conditions, proper route of administration, targeted delivery of exosomes to cardiac tissue, and difficulties with production and storage of exosomes in large numbers.