Cardiac telocytes — their junctions and functional implications

Abstract

Telocytes (TCs) form a cardiac network of interstitial cells. Our previous studies have shown that TCs are involved in heterocellular contacts with cardiomyocytes and cardiac stem/progenitor cells. In addition, TCs frequently establish ‘stromal synapses’ with several types of immunoreactive cells in various organs (www.telocytes.com). Using electron microscopy (EM) and electron microscope tomography (ET), we further investigated the interstitial cell network of TCs and found that TCs form ‘atypical’ junctions with virtually all types of cells in the human heart. EM and ET showed different junction types connecting TCs in a network (puncta adhaerentia minima, processus adhaerentes and manubria adhaerentia). The connections between TCs and cardiomyocytes are ‘dot’ junctions with nanocontacts or asymmetric junctions. Junctions between stem cells and TCs are either ‘stromal synapses’ or adhaerens junctions. An unexpected finding was that TCs have direct cell–cell (nano)contacts with Schwann cells, endothelial cells and pericytes. Therefore, ultrastructural analysis proved that the cardiac TC network could integrate the overall ‘information’ from vascular system (endothelial cells and pericytes), nervous system (Schwann cells), immune system (macrophages, mast cells), interstitium (fibroblasts, extracellular matrix), stem cells/progenitors and working cardiomyocytes. Generally, heterocellular contacts occur by means of minute junctions (point contacts, nanocontacts and planar contacts) and the mean intermembrane distance is within the macromolecular interaction range (10–30 nm). In conclusion, TCs make a network in the myocardial interstitium, which is involved in the long-distance intercellular signaling coordination. This integrated interstitial system appears to be composed of large homotropic zones (TC–TC junctions) and limited (distinct) heterotropic zones (heterocellular junctions of TCs).

Telocytes in normal and keratoconic human cornea: an immunohistochemical and transmission electron microscopy study

“…According to the possible functions which have been proposed for TC in a variety of organs 11, 12, 46, the regular distribution of TC and their telopodes that we observed throughout the whole normal corneal stroma might contribute to the correct assembly and maintenance of a highly organized collagenous matrix which is essential for conferring the adequate corneal transparency and mechanical stability. In addition, we found that in the normal cornea, TC establish homocellular contacts formed by gap junctions, highly specialized membrane structures which allow the exchange of small molecular mediators involved in intercellular signalling and thus contributing to the maintenance of tissue homoeostasis 38, 39. As suggested in other pathologies 23, 25, 26, 27, 28, 29, the reduction and loss of TC might therefore contribute to the altered organization of the ECM ultimately resulting into corneal dysfunction in keratoconus.…”

Ultrastructural identification of telocytes in the muscularis of chicken ileum

“…However, there is a requirement for the investigation of TC-specific biomarkers in order to clarify TC cell functionality and network biomarkers, to improve understanding of the interaction between proteins, genes, signaling pathways and dynamic networks, and to define and predict time-dependent TC function and morphological features (40,41). TCs also function in the vascular system, nervous system, immune system, interstitium and SC/progenitors (42). Manole et al (36) demonstrated that TCs are involved in neo-angiogenesis in experimental acute myocardial infarction.…”

A comprehensive guide to telocytes and their great potential in cardiovascular system

“…TCs may link with interstitial cells like fi broblasts, mast cells and macrophages by point contacts and planar junctions and with capillaries by point and planar contacts. Point contacts were also observed between TCs and basal lamina of Schwann cells (24).…”

“…They are usually localised between Tps, but intermittently this type of connection was observed between Tp and TC's cell body. TEM imaging showed that TCs are also connected with each other by a few types of adherens junctions: puncta adhaerentia minima, processus adhaerens (which joins overlapping Tps), recessus adhaerens (observed between two Tps and between Tp and cell body) and manubria adhaerentia (24).…”

“…TCs accompanying capillaries frequently establish heterocellular contacts with pericytes and endothelial cells. Those junctions were initially described as planar or point contacts, since no classic electron dense structures were found (24). No evidence has been found of direct connections between TCs and vascular smooth muscle cells (VSMCs) (47).…”