**1.1 The telocyte network**

The ability of these cells to form 3-D stromal networks can be considered a discriminant element for their recognition under the light microscope [8],

especially because no specific immunomarkers are available [28]. Indeed, the cell surface glycoprotein CD34, a marker shared with vascular endothelial cells, is currently considered one of the most suitable for the immunohistochemical identification of the TCs, which are also referred to as CD34+ stromal cells/TCs by some authors [29, 30]. Through extensive homo-cellular networks, TCs are believed to build the stromal scaffold whose continuity and adaptability guarantees the maintenance of the integrity of tissues/organs every time they are subjected to mechanical forces, such as distension and stretching. Moreover, TCs are universally considered key organizers of the connective tissue and eventually, they may contribute to the production and shaping of the extracellular matrix (ECM) in cooperation with fibroblasts. This has been observed in TCs located in the female genital tract where these cells express both estrogen and progesterone receptors [4, 31] whose activation is followed by significant changes of the TCs that acquire fibroblast-like features and become capable to produce the ECM [8]. Likely, the homo-cellular TCs contacts are also involved in the intercellular exchange of molecular or ionic signaling. Alongside the aforementioned roles, probably shared by all the TCs, many other roles have been attributed to these cells [30]. Therefore, each of the TCs subtypes is likely to play its organ-/tissue-specific role [8].

Although the TCs homo-cellular contacts are commonly observed, a variety of cell-to-cell contacts between TCs and other cell types (referred to as heterocellular contacts) are also observed [8, 32–35]. They consist of minute junctions (point contacts, nanocontacts, and planar contacts) whose mean inter-membrane distance is 10–30 nm, but more often by variably extended simple apposition of the contiguous plasma membranes that might act either as mechanical cell-to-cell attachments or as sites of intercellular communication [18]. Among these contacts, there are the so-called "stromal synapses" [36], a term used to describe those contacts occurring between TCs and several types of connective tissue cells such as mast cells, macrophages, myofibroblasts, and fibroblasts [8, 18, 35, 37]. The networks built by these hetero-cellular contacts are named "mixed networks." Collectively, the existence of mixed networks in addition to the homo-cellular TCs networks, the morphological and immunohistochemical differences reported for the TCs among organs and tissues, the existence of TCs subtypes, the interactions that TCs make with the ECM and, finally, the TCs vicinity to nerve endings and vascular cells, have substantiated the hypothesis that these cells may be part of integrated systems playing tissue-/organ-specific roles [8, 30, 32, 33, 35, 38].
