Telocytes and Their Extracellular Vesicles-Evidence and Hypotheses

Abstract

Entering the new millennium, nobody believed that there was the possibility of discovering a new cellular type. Nevertheless, telocytes (TCs) were described as a novel kind of interstitial cell. Ubiquitously distributed in the extracellular matrix of any tissue, TCs are regarded as cells with telopodes involved in intercellular communication by direct homo- and heterocellular junctions or by extracellular vesicle (EVs) release. Their discovery has aroused the interest of many research groups worldwide, and many researchers regard them as potentially regenerative cells. Given the experience of our laboratory, where these cells were first described, we review the evidence supporting the fact that TCs release EVs, and discuss alternative hypotheses about their future implications.

Keywords: ectosomes; exosomes; extracellular vesicles; telocytes; telopodes.

Figure 1

Schematic diagram of EVs transfer between cells, particularized for telocytes (TCs). Cells produce three types of extracellular vesicles (EVs): exosomes, ectosomes, and apoptotic bodies. The vesicles may be endocytosed, might fuse directly with the plasma membrane, or determine biological processes by ligand–receptor interactions on the cell surface. Arrows are indicative of the fact that the transfer is bidirectional and that EVs can shuttle between cells to communicate and exchange genetic material. Depending on the site of biogenesis, EVs’ heterogeneity, size, and composition are slightly different. ncRNA: non-coding RNA; miRNA: microRNA; MVB: multivesicular body.

Figure 2

Transmission electron microscopy (TEM) of a telocyte in human non-pregnant myometrium. (A) Two cellular bodies (TC1, TC2) can be easily seen in the interstitial space between smooth myocytes. One telocyte has long, convoluting telopodes (TC2). Scale bar = 5 μm; (B) Higher magnification detail of the area marked with a dotted square in (A). Note that the heterochromatin is mostly confined to the periphery of the nucleus, but is also dispersed throughout. Scale bar = 1.5 μm. TC: telocyte; Tp: telopode; SMC: smooth muscle cell; m: mitochondrion; rER: rough endoplasmic reticulum; N: nucleus; arrowhead: exosome; Ect: ectosome; arrow: cellular junction.

Figure 3

Transmission electron microscopy (TEM) of a telocyte in human non-pregnant myometrium. Image obtained by concatenation of seven microscopic fields. The telocyte exhibits a spindle-shape cell body, from where two extremely long telopodes are emerging. In the close proximity, other telopodes with tortuous trajectories contact the central telocyte by homo-cellular junctions, creating an intricate network. One can also observe numerous extracellular vesicles (arrowheads: exosomes; Ect: ectosomes) either shedding from or surrounding the telopodes. Arrows: cellular junctions; Tp(s) = telopode(s). Scale bar = 5 μm.

Figure 4

Focused ion beam scanning electron microscope (FIB-SEM) tomography. Three-dimensional reconstruction details of telopodes (Tps), from different viewing angles. (A) From this angle, four telopodes can be seen; (B) Tp2 has enlarged segments (podoms) alternating with slender segments; (C) Telopode with anfractuous contour. Extracellular vesicles appear in purple. Reproduced with permission from [35].

Figure 5

FIB-SEM of extracellular vesicle dynamics around a telocyte. (A–F) Six non-consecutive serial images depicting the biological fine structure of some EVs. Scale bar is 0.5 μm. Reproduced with permission from [35].

Figure 6

(A–D) FIB-SEM serial images of a human dermal telocyte presenting an extracellular vesicle (purple) budding from a podom. Note the empty appearance of the vesicle. Scale bar is 0.5 μm. Reproduced with permission from [35].