Myocardial interstitial Cajal‐like cells (ICLC) and their nanostructural relationships with intercalated discs: shed vesicles as intermediates

Abstract

Intercalated discs (ID) are complex junctional units that connect cardiac myocytes mechanically and electrochemically. However, there is limited information concerning the cardiomyocyte interaction with interstitial non-muscle cells. Our previous studies showed that myocardial interstitial Cajal-like cells (ICLC) are located in between cardiomyocytes, blood capillaries and nerve fibres. Typically, ICLC have several very long, moniliform, cytoplasmic processes which establish closed contacts with nerve fibres, as well as each other. We report here ultrastructural evidence concerning the relationships of ICLC processes with ID. The ICLC cytoplasmic prolongations (tens micrometers length) preferentially pass by or stop nearby the ID. Transmission electron microscopy emphasized three distinct connecting features between the tips of ICLC extensions and myocytes at the ‘mouth’ of ID: free or budding shed vesicles, exocytotic multi-vesicular bodies and direct contacts. In the last case, electron-dense repetitive nanostructures (‘pillars’) (35–40 nm high and 100–150 nm wide, similar to adhesion molecules) fasten the ICLC to the myocytes. All these features suggest a juxtacrine and/or paracrine intercellular mutual modulation of ICLC and cardiomyocytes in the microenvironment of ID, possibly monitoring the cardiac functions, particularly the electrical activity.

Ultrastructural and immunohistochemical characteristics of telocytes in the skin and skeletal muscle of newborn rats

“…Some vesicles may be intact and others are ruptured releasing their contents into the surrounding. Recently, evidence has come to light about the fact that TCs are able to release extracellular vesicles (Mandache et al, 2007;Manole et al, 2011;Popescu et al, 2011a,b,c;Cretoiu et al, 2013). They added that these vesicles might function as intercellular shuttles for biological signals.…”

“…Maintenance of tissue homeostasis and renewal, homo-and hetero-cellular junctions (Cretoiu et al, 2013) and also have the ability to release extracellular vesicles (Mandache et al, 2007;Fertig et al, 2014).…”

Telocytes

“…The cardiac TC have been hypothesized to play a nursing role (27) and those in the oviduct and myometrium to be sensors for steroid hormones (34,35). Significantly, the Tp establish homo-and heterocellular junctions (25); release shed vesicles and exosomes (26); and show paracrine secretion of IL6, VEGF, and NO. Thus TC, by sending macromolecular signals to neighboring cells, could influence their transcriptional activity.…”

“…wReproduced with permission from (27).x caveolae -the so-called Ca 2q uptake/release units. Tp establish several types of homo-and heterocellular junctions (Figure 3) (25), release shed vesicles and exosomes (Figure 1D)(26), have a dichotomous branching pattern forming a 3D labyrinthine network (Figures 1A and 2A), and might show adhesion plaques with the extracellular matrix(27).…”

Telocyte morphologies and potential roles in diseases

“…TCs have been identified in the interstitial space of many organs, including heart (Popescu et al, 2006;Mandache et al, 2007;Kostin and Popescu, 2009;, pericardium Suciu et al, 2009), pulmonary veins , intestine (Carmona et al, 2011), mesentery , gall bladder (Hinescu et al, 2007), uterus and fallopian tube (Popescu et al, 2005bCretoiu et al, 2009), trachea (Zheng et al, 2011), lungs (Zheng et al, 2011;Popescu et al, 2011a), pleura (Hinescu et al, 2011), skeletal muscle (Popescu et al, 2011b), exocrine pancreas (Popescu et al, 2005c), mammary gland (Gherghiceanu and Popescu, 2005;Popescu et al, 2005a;Radu et al, 2005), or placenta (Suciu et al, 2007(Suciu et al, , 2010. Recently, we firstly identified TCs in mouse trachea and successfully isolated and cultured TCs from mouse lung tissues (Zheng et al, 2011).…”