Extracellular Vesicles as Therapeutic Agents for Cardiac Fibrosis

FIGURE 1. Extracellular vesicle biology. Schematic of extracellular vesicle biogenesis. Exosomes arise from the fusion of inward budding of multivesicular bodies. The resulting vesicles are either degraded by lysosomes or secreted as exsomes. Microvesicles arise by direct budding from the plasma membrane and enter the extracellular space. Apoptotic bodies arise from membrane protrusions fragmentation of an apoptotic cell. ER, endoplasmic reticulum; ILV, intraluminal vesicle; MVB, multivesicular body.

FIGURE 2. Manifestations of cardiac fibrosis. Schematic of the three main types of cardiac fibrosis. Replacement fibrosis develops to fill necrotic lesions within the myocardium as a result of ischemia, infection, or trauma. Interstitial fibrosis develops in the interstitial space of the myocardium as a result of non-ischemic cardiomyopathies. Perivascular fibrosis develops in the peri-adventitial space as a result of non-ischemic cardiomyopathies.

FIGURE 3. Extracellular vesicle-mediated communication. Schematic of release and uptake of extracellular vesicles. Therapeutic cells secrete bioactive extracellular vesicles, which are taken up by diseased cells to alter cell function.

FIGURE 4. Therapeutic functions of extracellular vesicle cargo. Schematic of therapeutically active cargo found inside extracellular vesicles. Defined molecules exert specific biological functions in target tissues. EV, extracellular vesicle; ESC, embryonic stem cell; iPSC, induced pluripotent stem cell; miR, microRNA; EV-YF1, extracellular vesicle Y-RNA fragment.