A fresh hope for cardiac regeneration – exosomes and microRNA

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Improving tissue regeneration after myocardial infarction is an important goal in cardiovascular research, to reduce the risk of recurring infarction and heart failure. Cell replacement therapy using stem cells has long been thought to be a key for repairing the heart after injury, but many roadblocks stand in the way of turning this hope into reality. Embryonic stem cells differentiate into cardiomyocytes and improve cardiac function in animal models (source), but ethical concerns surrounding the use of human embryonic stem cells, as well as the risk of teratoma development and immune rejection, keep this type of therapy from the clinic. Induced pluripotent stem cells and other types of progenitor cells have also been attempted, but results have been mixed.

Enter a new study from Khan et al., published in Circulation Research, that describes a potential therapeutic avenue avoiding cell transplantation entirely. Exosomes are known to carry proteins and nucleic acids from cell to cell, serving as an intercellular communication system. In this study, Khan and colleagues found that exosomes derived from mouse embryonic stem cells carried members of the miR-290-295 cluster, especially miR-294, which led to greater survival and proliferation of cardiac progenitor cells. The overall effect of the exosomes on the infarcted tissue was greater neovascularization and reduced fibrosis, in addition to greater survival of the cardiomyocytes. (source)

Could the study of circulating microRNA hold promise for other cardiovascular diseases? The evidence suggests so. For example, in atherosclerosis, miR-126 in complex with Ago2 promotes turnover of vascular smooth muscle cells, contributing to the disease. However, in association with apoptotic bodies, miR-126 actually combats disease by inducing CXCL12, and is considered to have some therapeutic potential. Additionally, distinct profiles of HDL-associated miRNAs are seen in healthy individuals vs those with familial hypercholesteremia (miR-135a*, miR-188-5p, and miR-105 vs miR-223, miR-105, and miR-106a, respectively), lending insight into which miRNAs may be impacting this condition. (source)

A recent review also discussed the presence of so-called “cardiometabolic” miRNAs, miRNAs that contribute to development of atherosclerosis, ischemia-reperfusion injury, myocardial infarction or cardiac remodeling, in inflammatory microvesicles. These include let-7, associated with hypertension, miR-17/92, miR-126, and miR-133, among others, and further work will be required to see if they can be used as effective biomarkers. (source)

Whether as biomarkers or therapies, circulating miRNA will certainly continue to be a major player in cardiovascular research in the future. For more information about the roles of microRNAs in cardiovascular processes, check out the minireview, “miRNA regulation of angiogenesis: new roles for IGF-1R signaling and heparin.”

Ali Bierly

Ali Bierly, PhD is a Global Market Manager in Translational Sciences at QIAGEN, and has written on a number of scientific topics in the biotech industry as the author of QIAGEN's Reviews Online. She received her PhD from Cornell University in 2009, studying the immune response to a protozoan parasite, Toxoplasma gondii. Ali has a keen interest in the emerging importance of microRNA and other circulating nucleic acids as biomarkers for disease.

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