Extracellular vesicles release by cardiac telocytes: electron microscopy and electron tomography

Telocytes have been reported to play an important role in long-distance heterocellular communication in normal and diseased heart, both through direct contact (atypical junctions), as well as by releasing extracellular vesicles (EVs) which may act as paracrine mediators. Exosomes and ectosomes are the two main types of EVs, as classified by size and the mechanism of biogenesis. Using electron microscopy (EM) and electron tomography (ET) we have found that telocytes in culture release at least three types of EVs: exosomes (released from endosomes; 45 ± 8 nm), ectosomes (which bud directly from the plasma membrane; 128 ± 28 nm) and multivesicular cargos (MVC; 1 ± 0.4 μm), the latter containing tightly packaged endomembrane-bound vesicles (145 ± 35 nm). Electron tomography revealed that endomembrane vesicles are released into the extracellular space as a cargo enclosed by plasma membranes (estimated area of up to 3 μm(2)). This new type of EV, also released by telocytes in tissue, likely represents an essential component in the paracrine secretion of telocytes and may consequently be directly involved in heart physiology and regeneration.