Telocyte

Abstract: We used rat experimental myocardial infarction to study the ultrastructural recovery, especially neo-angiogenesis in the infarction border zone. We were interested in the possible role(s) of telocytes (TCs), a novel type of interstitial cell very recently discovered in myocardim (see http://www.telocytes.com). Electron microscopy, immunocytochemistry and analysis of several proangiogenic microRNAs provided evidence for TC involvement in neo-angiogenesis after myocardial infarction. Electron microscopy showed the close spatial association of TCs with neoangiogenetic elements. Higher resolution images provided the following information: (a) the intercellular space between the abluminal face of endothelium and its surrounding TCs is frequently less than 50 nm; (b) TCs establish multiple direct nanocontacts with endothelial cells, where the extracellular space seems obliterated; such nanocontacts have a length of 0.4–1.5 μm; (c) the absence of basal membrane on the abluminal face of endothelial cell. Besides the physical contacts (either nanoscopic or microscopic) TCs presumably contribute to neo-angiognesis via paracrine secretion (as shown by immunocytochemistry for VEGF or NOS2). Last but not least, TCs contain measurable quantities of angiogenic microRNAs (e.g. let-7e, 10a, 21, 27b, 100, 126-3p, 130a, 143, 155, 503). Taken together, the direct (physical) contact of TCs with endothelial tubes, as well as the indirect (chemical) positive influence within the ‘angiogenic zones’, suggests an important participation of TCs in neo-angiogenesis during the late stage of myocardial infarction.

Abstract: Skeletal muscle interstitium is crucial for regulation of blood flow, passage of substances from capillaries to myocytes and muscle regeneration. We show here, probably, for the first time, the presence of telocytes (TCs), a peculiar type of interstitial (stromal) cells, in rat, mouse and human skeletal muscle. TC features include (as already described in other tissues) a small cell body and very long and thin cell prolongations—telopodes (Tps) with moniliform appearance, dichotomous branching and 3D-network distribution. Transmission electron microscopy (TEM) revealed close vicinity of Tps with nerve endings, capillaries, satellite cells and myocytes, suggesting a TC role in intercellular signalling (via shed vesicles or exosomes). In situ immunolabelling showed that skeletal muscle TCs express c-kit, caveolin-1 and secrete VEGF. The same phenotypic profile was demonstrated in cell cultures. These markers and TEM data differentiate TCs from both satellite cells (e.g. TCs are Pax7 negative) and fibroblasts (which are c-kit negative). We also described non-satellite (resident) progenitor cell niche. In culture, TCs (but not satellite cells) emerge from muscle explants and form networks suggesting a key role in muscle regeneration and repair, at least after trauma.

Abstract: Telocytes (TC), a cell population located in the connective tissue of many organs of humans and laboratory mammals, are characterized by a small cell body and extremely long and thin processes. Different TC subpopulations share unique ultrastructural features, but express different markers. In the gastrointestinal (GI) tract, cells with features of TC were seen to be CD34-positive/c-kit-negative and several roles have been proposed for them. Other interstitial cell types with regulatory roles described in the gut are the c-kit-positive/CD34-negative/platelet-derived growth factor receptor α (PDGFRα)-negative interstitial cells of Cajal (ICC) and the PDGFRα-positive/c-kit-negative fibroblast-like cells (FLC). As TC display the same features and locations of the PDGFRα-positive cells, we investigated whether TC and PDGFRα-positive cells could be the same cell type. PDGFRα/CD34, PDGFRα/c-kit and CD34/c-kit double immunolabelling was performed in full-thickness specimens from human oesophagus, stomach and small and large intestines. All TC in the mucosa, submucosa and muscle coat were PDGFRα/CD34-positive. TC formed a three-dimensional network in the submucosa and in the interstitium between muscle layers, and an almost continuous layer at the submucosal borders of muscularis mucosae and circular muscle layer. Moreover, TC encircled muscle bundles, nerve structures, blood vessels, funds of gastric glands and intestinal crypts. Some TC were located within the muscle bundles, displaying the same location of ICC and running intermingled with them. ICC were c-kit-positive and CD34/PDGFRα-negative. In conclusion, in the human GI tract the TC are PDGFRα-positive and, therefore, might correspond to the FLC. We also hypothesize that in human gut, there are different TC subpopulations probably playing region-specific roles.

Abstract: Telocytes (TCs) have been described in various organs and species (www.telocytes.com) as cells with telopodes (Tps) – very long cellular extensions with an alternation of thin segments (podomers) and dilated portions (podoms). We examined TCs using electron microscopy (EM), immunohistochemistry (IHC), immunofluorescence (IF), time-lapse videomicroscopy and whole-cell patch voltage clamp. EM showed a three-dimensional network of dichotomous-branching Tps, a labyrinthine system with homocellular and heterocellular junctions. Tps release extracellular vesicles (mean diameter of 160.6±6.9 nm in non-pregnant myometrium and 171.6±4.6 nm in pregnant myometrium), sending macromolecular signals to neighbouring cells. Comparative measurements (non-pregnant and pregnant myometrium) of podomer thickness revealed values of 81.94±1.77 vs 75.53±1.81 nm, while the podoms' diameters were 268.6±8.27 vs 316.38±17.56 nm. IHC as well as IF revealed double c-kit and CD34 positive results. Time-lapse videomicroscopy of cell culture showed dynamic interactions between Tps and myocytes. In non-pregnant myometrium, patch-clamp recordings of TCs revealed a hyperpolarisation-activated chloride inward current with calcium dependence and the absence of L-type calcium channels. TCs seem to have no excitable properties similar to the surrounding smooth muscle cells (SMCs). In conclusion, this study shows the presence of TCs as a distinct cell type in human non-pregnant and pregnant myometrium and describes morphometric differences between the two physiological states. In addition, we provide a preliminary in vitro electrophysiological evaluation of the non-pregnant state, suggesting that TCs could influence timing of the contractile activity of SMCs.